Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the inju...Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.展开更多
OBJECTIVE A causal relationshiphas been postulated between cholinergic dysfunction and the progression of cognitive decline in neurodegenerative disorders. However,the cause of the cognitive dysfunction remains unclea...OBJECTIVE A causal relationshiphas been postulated between cholinergic dysfunction and the progression of cognitive decline in neurodegenerative disorders. However,the cause of the cognitive dysfunction remains unclear. METHODS Gab1^(loxP/loxP) were bred with ChAT-Cre mice to generate ChAT-Cre; Gab1^(f/f) mice. Excitability of cholinergic neurons wererecorded using whole-cel patch clump. A series of behavioral analyses were used to address the changes of cognitive function in ChAT-Cre; Gab1^(f/f) mice. Neurochemical changes on brain of conditional knockout mice were evaluated by using immunohistochemistry and Western blotting analysis. RESULTS Grb2-associated-binding protein 1(Gab1) is adocking/scaffolding molecule known to play an important role in cell growth and survival. Here,wereport that Gab1 is decreased in cholinergic neurons in a mousemodel of AD. We found that selective downregulation of Gab1 in the septum impaired learning and memory and hippocampal long-term potentiation,whereas overexpression of Gab1 in the same area rescued the cognitive deficitsseen in ChAT-Cre; Gab1^(f/f) and APP^(swe)/PS1 mice.^(18)F-FDGmicroP ET imaging data indicated that Gab1 treatment had no effect on metabolic activity of glucose in APPswe/PS1 mice. Moreover,we identify abnormal function of SKchannelscontributes to increased firing in cholinergic neuronsof ChAT-Cre; Gab1^(f/f) mice. CONCLUSION Gab1 signaling may serve as a potential treatment target for neurological disorders involving dysfunction of central cholinergic neurons.展开更多
Chondrocyte dysfunction has been demonstrated to be a major inducer of osteoarthritis(OA).The pathological mechanism of chondrocyte dysfunction is definitely multifactoral,but oxidative stressis regarded as one of the...Chondrocyte dysfunction has been demonstrated to be a major inducer of osteoarthritis(OA).The pathological mechanism of chondrocyte dysfunction is definitely multifactoral,but oxidative stressis regarded as one of the leading causes of apoptosis,autophagy,senescence,and mitochondrial dysfunctionin chondrocytes.Strategies for arresting oxidative stress-induced chondrocyte dysfunction have been considered as potential therapeutic targets for OA.Recently,fork head box O(Fox O)transcription factors have been determined to play a protective role in chondrocytes through the regulation of autophagy and defense against oxidative stress;they also regulate growth,maturation,and matrix synthesis.To explore Fox O′s potential role in the treatment of OA,we first discussed the recent advances in the field of oxidative stress-induced chondrocyte dysfunction and then emphasized the protective role of fox otranscription factors as a potential molecular target for the treatment of OA.Understanding the function of fox otranscription factors will be important in designing next-generation therapies to prevent or reverse the development of OA.展开更多
OBJECTIVE The Ca2+-activated Cl-channel(Ca CC)plays a crucial role in various physiological functions.Recent evidences suggest TMEM16A encodes CaC C in various cells,including endothelial cells.However,the role of TME...OBJECTIVE The Ca2+-activated Cl-channel(Ca CC)plays a crucial role in various physiological functions.Recent evidences suggest TMEM16A encodes CaC C in various cells,including endothelial cells.However,the role of TMEM16A in the vascular endothelial dysfunction in hypertension is unclear.METHODS In the study,RT-PCR,Western blotting,co-immunopricipitation,confocal imaging,patch-clamp,and endothelial-specific TMEM16A transgenic and knockout mice were employed.RESULTS We found that TMEM16A was expressed abundantly and functioned as Ca CC in endothelial cells.AngiotensinⅡ(AngⅡ)induced endothelial dysfunction with an increase in TMEM16A expression,which was alleviated by TMEM16A inhibitor.Further studies revealed that TMEM16A endothelial-specific knockout significantly lowered the blood pressure and ameliorated endothelial dysfunction in AngⅡ-induced hypertension,whereas,TMEM16A endothelial-specific overexpression showed the opposite effects.These results were related to the increased reactive oxygen species(ROS)generation,NADPH oxidase activation,and Nox2,p22phox expression facilitated by TMEM16A upon AngⅡ-induced hypertensive challenges.Moreover,TMEM16A directly interacted with Nox2 monomer and reduced the degradation of Nox2 through the proteasome-dependent endoplasmic recticulum-associated degradation pathway.TMEM16A also potentiated the translocation of p47phox and p67phox from cytosol to cell membrane and the subsequent interaction with Nox2.CONCLUSION Our results demonstrated that TMEM16A,as Ca CC,is a positive regulator of ROS generation via upregulating the activation of Nox2 NADPH oxidase in the vascular endothelium,and therefore facilitates endothelial dysfunction and hypertension.Modification of TMEM16A may be a novel therapeutic strategy for endothelial dysfunction-associated cardiovascular diseases.展开更多
OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchu...OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchusa italica(TFAI)exhibited potent cardioprotection on acute ischemia/reperfusion injured rats.This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction in mice and the underlying mechanism.METHODS Total flavonoids were extracted from the whole herb of Anchusa italica and were characterized using HPLC-MS analysis.The left anterior descending branch of coronary artery was ligated to induce myocardial infarction in mice.After surgery,the mice were orally fed with TFAI at the doses of 10,30 and 50 mg·kg-1 body mass per day for a total of four weeks.Cardiac function and infarct size were measured,and the levels of inflammatory mediators were detected.Hematoxylin and eosin(HE)stain and Masson Trichrome stain were performed.The apoptotic factors such as Bax,Bcl-2 and cleaved caspase 3 as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blotting.RESULTS The content of total flavonoids in TFAI was 56.2%.Four weeks following the MI surgery,TFAI enhanced the survival rate in post-MI mice.TFAI administration at the doses of 30 and 50 mg·kg-1 significantly reduced the infarct size and improved cardiac function indicated by elevated EF and FS.Assay of inflammation factors showed that the sera levels of TNF-α,IL-1β and IL-6 were significantly decreased by TFAI treatment as compared to the MI group.HE stain and Masson Trichrome stain demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis indicated by decreased cross-section area and collagen volume.Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were signifi⁃cantly downregulated following TFAI treatment.Additionally,TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway.CONCLUSION TFAI exerts a protective effect against chronic myocardial infarction and its beneficial effects on cardiac function and cardiac remodeling might be at least attributable to anti-inflammation and suppression of the PI3K/Akt/mTOR signaling pathway.展开更多
Intra-aortic balloon pump (IABP)support is used in severalclinical situations.To determine its efficacy in patients with severe heartfailure awaiting cardiac transplantation,the experience at the Universityof Pittsbur...Intra-aortic balloon pump (IABP)support is used in severalclinical situations.To determine its efficacy in patients with severe heartfailure awaiting cardiac transplantation,the experience at the Universityof Pittsburgh from May 1986 to October 1989 was reviewed.Of 392 patientson the waiting list,(16.3%) required IABP.All had previously been oninotropic support for varying periods of time.The ability to stabilize andto sustain the patient to cardiac transplantation was 75%.Twenty patients(31.3% of group) required and were provided more extensive mechanicalzsupport with either total artificial heart (n=ll) or left ventrieular assistdevice (n =9).Twenty-nine patients (45% of entire gronp) were able tohave the IABP removed prior to transplantation.Seventeen patients(26.6%)parameters demonstrated improvement with IABP.These data support IABPas a bridge to transplantation in patients with severe heart failure who havenot been stabilized on inotropie agents alone.These data also demonstratethat IABP support may only be required temporarily in a subgroup of pa-tients awaiting cardiac transplantation.展开更多
Objective to explore the molecular mechanism of carvedilol effect on fetal energy metabolism during the development of cardiac hypertrophy. Methods Male Wistar rats were divided into the coarctation of abdominal aorta...Objective to explore the molecular mechanism of carvedilol effect on fetal energy metabolism during the development of cardiac hypertrophy. Methods Male Wistar rats were divided into the coarctation of abdominal aorta group (CAA), sham operation group (SH), and carvedilol intervention group (CAR+CAA, carvedilol 30mg·kg -1 ·day -1 orally) and carvedilol control group (CAR+SH). Hemodynamics, ventricular remodeling parameters, free fatty acid in blood serum and cardiac myocyte, RT PCR analysis of the expressions of Muscle Carnitine Palmitoyltransferase I (M CPT I) and Medium Chain Acyl CoA Dehydrogenase (MCAD) mRNA were measured in all rats at 16 week after operation. Results Left ventricular hypertrophy occurrd after operation 16 weeks in group of CAA, accompanying with plasma free fatty acids accumulation, and both the levels of M CPT I and MCADmRNA were decreased significantly ( P <0.05). Carvedilol can reduce the left ventricular hypertrophy induced by pressure overload. The gene expressions of rate limiting enzyme(M CPT I) and key enzyme of fatty acid (MCAD) were upregulated in the CAR+CAA group, comparing with CAA group ( P <0.05). There was no statistically significant difference between SH group and CAR + SH group. Pressure overload in CAA rats downregulates the gene expression of rate limiting enzyme and key enzyme of fatty acid oxidation. Conclusions The intervention with carvedilol may attenuates the reversion of the metabolic gene expression back towards fetal type through up regulating the expression of M CPT I and MCADmRNA. Thus, carvedilol may confer cardioprotective effects in heart failure partly by preserving of the normal metabolic gene regulation.展开更多
OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model ...OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model group(SHR,receive distilled water)and SF treatment groups(SF 20,40 and 80 mg·kg^-1 per day,respectively).Age-matched male Wistar-Kyoto(WKY)rats gavaged with distilled water served as controls.After 12 weeks of treatment,the effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement,pathological analysis and the expression of atrial natriuretic peptide(ANP),myosin heavy chainβ(β-MHC)-a gene related to myocardial hypertrophy.In order to explore the mechanism of SF on myocardial hypertrophy,the calcium-sensing receptor(CaSR),calcineurin(CaN),nuclear factor of activated T cell 3(NFAT3),phosphorylation NFAT3(p-NFAT3),zinc finger transcription factor(GATA4),phosphorylation GATA4(p-GATA4),protein kinase Cβ(PKC-β),Raf-1,extracellular regulated protein kinase 1/2(ERK 1/2),phosphorylation ERK1/2(p-ERK 1/2)and mitogen-activated protein kinase phosphatase-1(MKP-1)were detected.RESULTS The myocardial hypertrophy parameters,myocardial cell cross section area,left ventricular wall thickness and expression of ANP and β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 were significantly increased,while the left ventricular cavity was significantly smaller,expression of p-NFAT3 and MKP-1 were significantly decreased,meanwhile,the ultra⁃structure of cardiomyocytes was significantly damaged in 26-week-old SHR rats.Notably,SF significantly ameliorated myocardial hyper⁃trophy in 26-week-old SHR rats;suppressed the overexpression of ANP,β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 and increased the expression of p-NFAT3 and MKP-1.CONCLUSION SF can inhibit cardiac hypertrophy in SHR rats,and the mechanism may be related to the inhibition of CaSR mediated signaling pathway.展开更多
Aim To explore the role of transcription factor Foxp3 and the regulating effect of triptolide （TP） in the progression of myocardial hypertrophy in mice. Methods Fifty male mice were randomly divided into 5 groups, i...Aim To explore the role of transcription factor Foxp3 and the regulating effect of triptolide （TP） in the progression of myocardial hypertrophy in mice. Methods Fifty male mice were randomly divided into 5 groups, i. e., normal control group, myocardial hypertrophy model group and TP （10, 30, 90μg · kg^-1） treated groups. Myocardial hypertrophy was induced by isoprenaline （ISO） 5 mg kg^-1 once daily for 14 days. Triptolide was giv- en intraperitoneally once daily. Left ventricle tissue was subjected to HE staining and chemiluminescence technique to assess effects on hypertrophy, fibrosis and inflammation, quantitative assessment of hypertrophy regulatory genes were performed by qPCR and WB. Results After 14 days of treatment, myocardial expressions of Foxp3 and CD4 were significantly reduced in the model group compared with controls. The expression level of TGFβ1 in control group was lower, while that in model group increased obviously. TP could significantly lessen myocardial tissue damage, and reduce the heart index and left ventricular index. Compared with model group, TP （30, 90 μg · kg^-1 ） significantly increased myocardial expression ratio of α-MHC to β-MHC, reduced serumal levels of BNP and troponin I, elevated mRNA and protein expressions of Foxp3 and CD4 in myocardial tissue and reduced the protein expression of TGFβ1 by comparison of those in model group. Conclusion TP can effectively ameliorate myocardial damage and inhibit left ventricular remodeling through elevating the expression of CD4 and Foxp3 and decreasing that of TGF-β.展开更多
Objective Despite dramatic advances in surgical technique and perioperative care,some children still suffered serious adverse event in early postoperative period which were associated with increased morbidity and mort...Objective Despite dramatic advances in surgical technique and perioperative care,some children still suffered serious adverse event in early postoperative period which were associated with increased morbidity and mortality.There was little information regarding the impact of adverse events on the postoperative recovery,especially the serious adverse events occurring immediately after surgery.We sought to evaluate the early postoperative serious adverse events and examine the impact of them on postoperative recovery.展开更多
Objective Vasopressin has showed a beneficial use in pediatric patients with vasodilatory shock after cardiac surgery. However, the optimal timing of vasopressin initiation has not been investigated.Our aim was to eva...Objective Vasopressin has showed a beneficial use in pediatric patients with vasodilatory shock after cardiac surgery. However, the optimal timing of vasopressin initiation has not been investigated.Our aim was to evaluate the effect of early vasopressin initiation for these patients.展开更多
Objective Overactivation of sympathetic nerve system is one of the main mechanism in post-MI myocardial remodeling even after early reperfusion, it eventually leads to heart failure. And renal denervation which target...Objective Overactivation of sympathetic nerve system is one of the main mechanism in post-MI myocardial remodeling even after early reperfusion, it eventually leads to heart failure. And renal denervation which targets at renal sympathetic nerves may have beneficial effects on cardiac remodeling. So we perform an experiment aiming to investigate the effect of RDN on cardiac remodeling and function.展开更多
Objective Patients undergoing cardiac surgery are exposed to a large range of drugs and foreign substances,which might result in anaphylaxis.Severe anaphylaxis in cardiac surgical patients could be life-threatening.Th...Objective Patients undergoing cardiac surgery are exposed to a large range of drugs and foreign substances,which might result in anaphylaxis.Severe anaphylaxis in cardiac surgical patients could be life-threatening.Therefore,timely diagnosis and proactive treatment are crucial.Definition of anaphylaxis,epidemiology of anaphylaxis and common allergens,specific anaphylaxis,diagnosis and management of peri-operative anaphylaxis in cardiac surgery patients were discussed in this review.展开更多
OBJECTIVE To investigate the effects of Huanglian Jiedu decoction on cognitive dysfunction of zebrafish with Alzheimer disease.METHODS 126 g of coptis chinensis,84 g of phellorescent phellorescent chinensis,84 g of sc...OBJECTIVE To investigate the effects of Huanglian Jiedu decoction on cognitive dysfunction of zebrafish with Alzheimer disease.METHODS 126 g of coptis chinensis,84 g of phellorescent phellorescent chinensis,84 g of scutellaria chinensis and 126 g of gardenia chinensis were immersed in 10,8 and 8 times of water for 30 min,and then extracted at 100℃for 2,1.5 and 1.5 h,respectively.The three extracts were coarse filtered and concentrated into 308 g·L-1 and stored in refrigerator for later use.200 zebrafish were selected for behavioral train⁃ing in T-shaped tank for seven days.After that,the behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis.Qualified zebrafish were selected as the blank group.Except for the blank group,zebrafish in the other 5 groups were exposed to AlCl3100μg·L-1 aquaculture water for modeling,and exposed for 6 d.The behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis,and Select the successfully modeled zebraf⁃ish.After that,huperzine A(4μg·L-1)and Huan⁃glian Jiedu decoction of low,medium and high doses(154,308 and 616 mg·L-1)were adminis⁃tered respectively,and exposed for six days.Then,the behavior analysis was conducted again through the behavioral record analysis soft⁃ware Smart 3.0 to select qualified zebrafish.After the training,the brain and gut of zebrafish in each group were collected,and the expression changes of N-cadherin,p-P38/p38MAPK and p-Tau in the brain were detected by Western blot⁃ting and qPCR to show the effect of Huanglian Jiedu decoction on cognitive dysfunction of Zebrafish with Alzheimer disease.RESULTS Western blotting and qPCR results showed that the contents of N-cadherin increased(P<0.05),and the contents of p-P38/p38MAPK and p-Tau decreased(P<0.05)compared with the model group,indicating that Huanglian Jiadu decoction had an effect on the cognitive dysfunction of zebrafish with Alzheimer disease.CONCLU⁃SION Huanglian Jiedu decoction can alleviate cognitive dysfunction of zebrafish model with Alzheimer disease to a certain extent.展开更多
Objective:To assess the correlation of signs of myocardial damage to serum cardiac troponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated ne...Objective:To assess the correlation of signs of myocardial damage to serum cardiac troponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated neonates and 25 controls at 12 h of age by immunoassay.The asphyxiated neonates were followed up until discharge or death.Results:Asphyxiated neonates had significantly higher concentrations of cTnI and CK-MB than controls(P<0.001).Serum cTnI concentrations were significantly higher in asphyxiated neonates who developed hypotension,heart failure or those had low ejection fraction(P<0.01).Serum cTnI concentrations were significantly higher in asphyxiated who died than those who survived(P<0.01).There was no significant difference in serum CK-MB mass concentrations between asphyxiated neonates with and without these complications.Conclusion:Unlike CK-MB,serum cTnI concentrations are significantly higher in asphyxiated neonates who died or developed cardiac dysfunction.展开更多
Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading t...Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.展开更多
Current pharmacological therapies used in clinical practice for individuals with cardiac, hepatic, renal or pulmonary fibrosis do not show desirable effects; therefore, new targets of therapy are urgently required. Mi...Current pharmacological therapies used in clinical practice for individuals with cardiac, hepatic, renal or pulmonary fibrosis do not show desirable effects; therefore, new targets of therapy are urgently required. Mitochon- dria play pivotal role in energy production, metabolism, serving as storage tanks of calcium ions and cell fate deter- mination. Recent results of our experiments and other authors＇ studies suggest that the electron transport chain dys- function, electron leakage increasing, the accumulation of fragmented mitochondria, and the impairment in the mi- tophagy system contribute to pathogenesis of tissue fibrosis. Mitochondria targeting compounds exert promise in trea- ring and attenuating the progress of these diseases, indicating potential strategies to target mitochondria in the treat- ment of tissue fibrosis.展开更多
OBJECTIVE To evaluate the effects of flavonoids from Xindakang(Hippophae Fructus flavone)on myocardial systolic and diastolic functions of isolated frog hearts and explore the possible mechanism,and provide experiment...OBJECTIVE To evaluate the effects of flavonoids from Xindakang(Hippophae Fructus flavone)on myocardial systolic and diastolic functions of isolated frog hearts and explore the possible mechanism,and provide experimental basis for improving the effect and efficacy of Xindakang on cardiac function.METHODS The isolated frog heart perfusion specimens were prepared by Yagi′s method,and the effects of different concentrations of Xindakang on myocardial contractility(0.0125,0.025,0.05,0.1 and 0.2 g·L^(-1)),heart rate and cardiac output of isolated frog heart were studied.Acetylcholine,atropine and epinephrine were administered successively to analyze the effects of Xindakang on cardiac systolic function of isolated frogs under the action of different drugs,and compared with propranolol.The effect of extracellular calcium ion concentration on the action of Xindakang was studied by using low calcium concentration,high calcium concentration and normal Ren′s solution.To study the effect and possible mechanism of Xindakang on cardiac systolic function of frog.RESULTS The concentration of Xindakang in the range of 0.0125-0.1 g·L^(-1)could weaken the contractility of isolated frog heart and increase the concentration of Xindakang.The inhibitory effect of Xindakang on contractility of isolated frog heart was enhanced,and showed obvious dose-effect relationship.Cardiac output was significantly decreased by Xindakang(P<0.01),slow heart rate(P<0.05);M receptor blocker atropine could not antagonize the contractile effect of Xindakang,and Xindakang could not completely antagonize the contractile effect of adrenalin.Xindakang could inhibit the isolated frog heart in low calcium concentration,high calcium concentration and normal Ren′s solution,and increased with the increase of extracellular calcium concentration(P<0.01).CONCLUSION Xindakang has inhibitory effect on isolated frog heart,which may be achieved by blocking the calcium channel on myocardial cell membrane and reducing the calcium concentration in myocardial cells.展开更多
Aim As we all know, apelin acts as the endogenous ligand of APJ, being a member of G protein cou- pled receptors family, apelin/APJ system is involved in plentiful diseases and extremely responsible for the occur- ren...Aim As we all know, apelin acts as the endogenous ligand of APJ, being a member of G protein cou- pled receptors family, apelin/APJ system is involved in plentiful diseases and extremely responsible for the occur- rence and the development of cardiovascular diseases, among many kinds of heart diseases, it is the cardiac hyper- trophy that catches our attention. The myocardial expression of apelin/APJ decreased in rats with left ventrieular hypertrophy suggesting us there is a link between apelin and cardiac hypertrophy. Furthermore, it has been repor- ted that apelin is able to alleviate cardiac hypertrophy induced by Ang II, H202 and exercise. Nevertheless, our la- boratory discovered that apelin is certain to induce cardiac hypertrophy through PI3k-Akt-ERK1/2-p70S6K pathway or via up-regulating the levels of ROS to cause oxidative stress. The above-mentioned contradiction indicates us apelin may have dual effects in cardiac hypertrophy. Moreover, we also illuminate that apelin is involved in some diseases such as obesity, diabetes, hypertension, myoearditis and myocardial infarction, eoineidentally, all these diseases are associated with cardiac hypertrophy. Therefore, this review is aim to unveil the intricate relationship between apelin and cardiac hypertrophy.展开更多
Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely assoc...Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely associated with cognitive impairment.Therefore,this research aimed to explore whether the HMGB1/TLR4 pathway involves in chronic stress-induced cognitive dysfunction.Methods The chronic unpredictable mild stress(CUMS)mouse model was established by randomly giving different types of stress every day for four consecutive weeks.Cognitive function was detected by novel object recognition test,Y-maze test,and Morris water maze test.The protein expressions of HMGB1,TLR4,B-cell lymphoma 2(BCL2),and BCL2 associated X(BAX)were determined by Western blot.The damage of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin(HE)staining.Results The protein expressions of HMGB1 and TLR4 were significantly increased in the hippocampus of chronic stress mice.Furthermore,inhibition of the HMGB1/TLR4 pathway induced by ethyl pyruvate(EP,a specific inhibitor of HMGB1)and TAK242(a selective inhibitor of TLR4)treatment attenuated cognitive impairment in chronic stress mice,according to the novel object recognition test,Y-maze test,and Morris water maze test.In addition,administration of EP and TAK242 also mitigated the increase of apoptosis in the hippocampus of chronic stress mice.Conclusion These results indicate that the hippocampal HMGB1/TLR4 pathway contributes to chronic stress-induced apoptosis and cognitive dysfunction.展开更多
基金supported by the National Key Research and Development Program(2021YFC3002205)the Postgraduate Research and Innovation Program of Tianjin Municipal Education Commission(2022BKY113),China.
文摘Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
文摘OBJECTIVE A causal relationshiphas been postulated between cholinergic dysfunction and the progression of cognitive decline in neurodegenerative disorders. However,the cause of the cognitive dysfunction remains unclear. METHODS Gab1^(loxP/loxP) were bred with ChAT-Cre mice to generate ChAT-Cre; Gab1^(f/f) mice. Excitability of cholinergic neurons wererecorded using whole-cel patch clump. A series of behavioral analyses were used to address the changes of cognitive function in ChAT-Cre; Gab1^(f/f) mice. Neurochemical changes on brain of conditional knockout mice were evaluated by using immunohistochemistry and Western blotting analysis. RESULTS Grb2-associated-binding protein 1(Gab1) is adocking/scaffolding molecule known to play an important role in cell growth and survival. Here,wereport that Gab1 is decreased in cholinergic neurons in a mousemodel of AD. We found that selective downregulation of Gab1 in the septum impaired learning and memory and hippocampal long-term potentiation,whereas overexpression of Gab1 in the same area rescued the cognitive deficitsseen in ChAT-Cre; Gab1^(f/f) and APP^(swe)/PS1 mice.^(18)F-FDGmicroP ET imaging data indicated that Gab1 treatment had no effect on metabolic activity of glucose in APPswe/PS1 mice. Moreover,we identify abnormal function of SKchannelscontributes to increased firing in cholinergic neuronsof ChAT-Cre; Gab1^(f/f) mice. CONCLUSION Gab1 signaling may serve as a potential treatment target for neurological disorders involving dysfunction of central cholinergic neurons.
基金supported by National Natural Science Foundation of China(81560662)China Postdoctoral Science Foundation(2017M610543)
文摘Chondrocyte dysfunction has been demonstrated to be a major inducer of osteoarthritis(OA).The pathological mechanism of chondrocyte dysfunction is definitely multifactoral,but oxidative stressis regarded as one of the leading causes of apoptosis,autophagy,senescence,and mitochondrial dysfunctionin chondrocytes.Strategies for arresting oxidative stress-induced chondrocyte dysfunction have been considered as potential therapeutic targets for OA.Recently,fork head box O(Fox O)transcription factors have been determined to play a protective role in chondrocytes through the regulation of autophagy and defense against oxidative stress;they also regulate growth,maturation,and matrix synthesis.To explore Fox O′s potential role in the treatment of OA,we first discussed the recent advances in the field of oxidative stress-induced chondrocyte dysfunction and then emphasized the protective role of fox otranscription factors as a potential molecular target for the treatment of OA.Understanding the function of fox otranscription factors will be important in designing next-generation therapies to prevent or reverse the development of OA.
基金The project supported by National Natural Science Foundation of China(81230082,81302771,81525025,81573422,81500226)Natural Science Foundation of Guangdong Province(2014A030313087)by Science and Technology program of Guangzhou City(201607010255)
文摘OBJECTIVE The Ca2+-activated Cl-channel(Ca CC)plays a crucial role in various physiological functions.Recent evidences suggest TMEM16A encodes CaC C in various cells,including endothelial cells.However,the role of TMEM16A in the vascular endothelial dysfunction in hypertension is unclear.METHODS In the study,RT-PCR,Western blotting,co-immunopricipitation,confocal imaging,patch-clamp,and endothelial-specific TMEM16A transgenic and knockout mice were employed.RESULTS We found that TMEM16A was expressed abundantly and functioned as Ca CC in endothelial cells.AngiotensinⅡ(AngⅡ)induced endothelial dysfunction with an increase in TMEM16A expression,which was alleviated by TMEM16A inhibitor.Further studies revealed that TMEM16A endothelial-specific knockout significantly lowered the blood pressure and ameliorated endothelial dysfunction in AngⅡ-induced hypertension,whereas,TMEM16A endothelial-specific overexpression showed the opposite effects.These results were related to the increased reactive oxygen species(ROS)generation,NADPH oxidase activation,and Nox2,p22phox expression facilitated by TMEM16A upon AngⅡ-induced hypertensive challenges.Moreover,TMEM16A directly interacted with Nox2 monomer and reduced the degradation of Nox2 through the proteasome-dependent endoplasmic recticulum-associated degradation pathway.TMEM16A also potentiated the translocation of p47phox and p67phox from cytosol to cell membrane and the subsequent interaction with Nox2.CONCLUSION Our results demonstrated that TMEM16A,as Ca CC,is a positive regulator of ROS generation via upregulating the activation of Nox2 NADPH oxidase in the vascular endothelium,and therefore facilitates endothelial dysfunction and hypertension.Modification of TMEM16A may be a novel therapeutic strategy for endothelial dysfunction-associated cardiovascular diseases.
基金CAMS Innovation Fund for Medical Sciences(CIFMS)318(2016-I2M-3-007)National Natural Science Foundation of China(81673422and 81202538)
文摘OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchusa italica(TFAI)exhibited potent cardioprotection on acute ischemia/reperfusion injured rats.This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction in mice and the underlying mechanism.METHODS Total flavonoids were extracted from the whole herb of Anchusa italica and were characterized using HPLC-MS analysis.The left anterior descending branch of coronary artery was ligated to induce myocardial infarction in mice.After surgery,the mice were orally fed with TFAI at the doses of 10,30 and 50 mg·kg-1 body mass per day for a total of four weeks.Cardiac function and infarct size were measured,and the levels of inflammatory mediators were detected.Hematoxylin and eosin(HE)stain and Masson Trichrome stain were performed.The apoptotic factors such as Bax,Bcl-2 and cleaved caspase 3 as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blotting.RESULTS The content of total flavonoids in TFAI was 56.2%.Four weeks following the MI surgery,TFAI enhanced the survival rate in post-MI mice.TFAI administration at the doses of 30 and 50 mg·kg-1 significantly reduced the infarct size and improved cardiac function indicated by elevated EF and FS.Assay of inflammation factors showed that the sera levels of TNF-α,IL-1β and IL-6 were significantly decreased by TFAI treatment as compared to the MI group.HE stain and Masson Trichrome stain demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis indicated by decreased cross-section area and collagen volume.Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were signifi⁃cantly downregulated following TFAI treatment.Additionally,TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway.CONCLUSION TFAI exerts a protective effect against chronic myocardial infarction and its beneficial effects on cardiac function and cardiac remodeling might be at least attributable to anti-inflammation and suppression of the PI3K/Akt/mTOR signaling pathway.
文摘Intra-aortic balloon pump (IABP)support is used in severalclinical situations.To determine its efficacy in patients with severe heartfailure awaiting cardiac transplantation,the experience at the Universityof Pittsburgh from May 1986 to October 1989 was reviewed.Of 392 patientson the waiting list,(16.3%) required IABP.All had previously been oninotropic support for varying periods of time.The ability to stabilize andto sustain the patient to cardiac transplantation was 75%.Twenty patients(31.3% of group) required and were provided more extensive mechanicalzsupport with either total artificial heart (n=ll) or left ventrieular assistdevice (n =9).Twenty-nine patients (45% of entire gronp) were able tohave the IABP removed prior to transplantation.Seventeen patients(26.6%)parameters demonstrated improvement with IABP.These data support IABPas a bridge to transplantation in patients with severe heart failure who havenot been stabilized on inotropie agents alone.These data also demonstratethat IABP support may only be required temporarily in a subgroup of pa-tients awaiting cardiac transplantation.
文摘Objective to explore the molecular mechanism of carvedilol effect on fetal energy metabolism during the development of cardiac hypertrophy. Methods Male Wistar rats were divided into the coarctation of abdominal aorta group (CAA), sham operation group (SH), and carvedilol intervention group (CAR+CAA, carvedilol 30mg·kg -1 ·day -1 orally) and carvedilol control group (CAR+SH). Hemodynamics, ventricular remodeling parameters, free fatty acid in blood serum and cardiac myocyte, RT PCR analysis of the expressions of Muscle Carnitine Palmitoyltransferase I (M CPT I) and Medium Chain Acyl CoA Dehydrogenase (MCAD) mRNA were measured in all rats at 16 week after operation. Results Left ventricular hypertrophy occurrd after operation 16 weeks in group of CAA, accompanying with plasma free fatty acids accumulation, and both the levels of M CPT I and MCADmRNA were decreased significantly ( P <0.05). Carvedilol can reduce the left ventricular hypertrophy induced by pressure overload. The gene expressions of rate limiting enzyme(M CPT I) and key enzyme of fatty acid (MCAD) were upregulated in the CAR+CAA group, comparing with CAA group ( P <0.05). There was no statistically significant difference between SH group and CAR + SH group. Pressure overload in CAA rats downregulates the gene expression of rate limiting enzyme and key enzyme of fatty acid oxidation. Conclusions The intervention with carvedilol may attenuates the reversion of the metabolic gene expression back towards fetal type through up regulating the expression of M CPT I and MCADmRNA. Thus, carvedilol may confer cardioprotective effects in heart failure partly by preserving of the normal metabolic gene regulation.
基金National Natural Science Foundation of China(81860732)Scientific and Technological Projects for Social Development in Guizhou Province of China([2011]3036)the State Key Laboratory of Cardiovascular Disease(2017kf-03)
文摘OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model group(SHR,receive distilled water)and SF treatment groups(SF 20,40 and 80 mg·kg^-1 per day,respectively).Age-matched male Wistar-Kyoto(WKY)rats gavaged with distilled water served as controls.After 12 weeks of treatment,the effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement,pathological analysis and the expression of atrial natriuretic peptide(ANP),myosin heavy chainβ(β-MHC)-a gene related to myocardial hypertrophy.In order to explore the mechanism of SF on myocardial hypertrophy,the calcium-sensing receptor(CaSR),calcineurin(CaN),nuclear factor of activated T cell 3(NFAT3),phosphorylation NFAT3(p-NFAT3),zinc finger transcription factor(GATA4),phosphorylation GATA4(p-GATA4),protein kinase Cβ(PKC-β),Raf-1,extracellular regulated protein kinase 1/2(ERK 1/2),phosphorylation ERK1/2(p-ERK 1/2)and mitogen-activated protein kinase phosphatase-1(MKP-1)were detected.RESULTS The myocardial hypertrophy parameters,myocardial cell cross section area,left ventricular wall thickness and expression of ANP and β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 were significantly increased,while the left ventricular cavity was significantly smaller,expression of p-NFAT3 and MKP-1 were significantly decreased,meanwhile,the ultra⁃structure of cardiomyocytes was significantly damaged in 26-week-old SHR rats.Notably,SF significantly ameliorated myocardial hyper⁃trophy in 26-week-old SHR rats;suppressed the overexpression of ANP,β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 and increased the expression of p-NFAT3 and MKP-1.CONCLUSION SF can inhibit cardiac hypertrophy in SHR rats,and the mechanism may be related to the inhibition of CaSR mediated signaling pathway.
文摘Aim To explore the role of transcription factor Foxp3 and the regulating effect of triptolide （TP） in the progression of myocardial hypertrophy in mice. Methods Fifty male mice were randomly divided into 5 groups, i. e., normal control group, myocardial hypertrophy model group and TP （10, 30, 90μg · kg^-1） treated groups. Myocardial hypertrophy was induced by isoprenaline （ISO） 5 mg kg^-1 once daily for 14 days. Triptolide was giv- en intraperitoneally once daily. Left ventricle tissue was subjected to HE staining and chemiluminescence technique to assess effects on hypertrophy, fibrosis and inflammation, quantitative assessment of hypertrophy regulatory genes were performed by qPCR and WB. Results After 14 days of treatment, myocardial expressions of Foxp3 and CD4 were significantly reduced in the model group compared with controls. The expression level of TGFβ1 in control group was lower, while that in model group increased obviously. TP could significantly lessen myocardial tissue damage, and reduce the heart index and left ventricular index. Compared with model group, TP （30, 90 μg · kg^-1 ） significantly increased myocardial expression ratio of α-MHC to β-MHC, reduced serumal levels of BNP and troponin I, elevated mRNA and protein expressions of Foxp3 and CD4 in myocardial tissue and reduced the protein expression of TGFβ1 by comparison of those in model group. Conclusion TP can effectively ameliorate myocardial damage and inhibit left ventricular remodeling through elevating the expression of CD4 and Foxp3 and decreasing that of TGF-β.
文摘Objective Despite dramatic advances in surgical technique and perioperative care,some children still suffered serious adverse event in early postoperative period which were associated with increased morbidity and mortality.There was little information regarding the impact of adverse events on the postoperative recovery,especially the serious adverse events occurring immediately after surgery.We sought to evaluate the early postoperative serious adverse events and examine the impact of them on postoperative recovery.
文摘Objective Vasopressin has showed a beneficial use in pediatric patients with vasodilatory shock after cardiac surgery. However, the optimal timing of vasopressin initiation has not been investigated.Our aim was to evaluate the effect of early vasopressin initiation for these patients.
文摘Objective Overactivation of sympathetic nerve system is one of the main mechanism in post-MI myocardial remodeling even after early reperfusion, it eventually leads to heart failure. And renal denervation which targets at renal sympathetic nerves may have beneficial effects on cardiac remodeling. So we perform an experiment aiming to investigate the effect of RDN on cardiac remodeling and function.
文摘Objective Patients undergoing cardiac surgery are exposed to a large range of drugs and foreign substances,which might result in anaphylaxis.Severe anaphylaxis in cardiac surgical patients could be life-threatening.Therefore,timely diagnosis and proactive treatment are crucial.Definition of anaphylaxis,epidemiology of anaphylaxis and common allergens,specific anaphylaxis,diagnosis and management of peri-operative anaphylaxis in cardiac surgery patients were discussed in this review.
基金National Natural Science Foundation of china(8216140711)Natural Science Foundation of Guangxi Province(2017GXNSFAA198255)+2 种基金Natural Science Foun⁃dation of Guangxi Province(2018GXNSFBA138028)Open Project Program of Guangxi Key Laboratory of Brain and Cognitive Neuroscience,GuilinMedicalUniversity(GKLBCN-20180105-03)and 2019 College Student Innovation and Entre⁃preneurship Project Training Program(201910601038)。
文摘OBJECTIVE To investigate the effects of Huanglian Jiedu decoction on cognitive dysfunction of zebrafish with Alzheimer disease.METHODS 126 g of coptis chinensis,84 g of phellorescent phellorescent chinensis,84 g of scutellaria chinensis and 126 g of gardenia chinensis were immersed in 10,8 and 8 times of water for 30 min,and then extracted at 100℃for 2,1.5 and 1.5 h,respectively.The three extracts were coarse filtered and concentrated into 308 g·L-1 and stored in refrigerator for later use.200 zebrafish were selected for behavioral train⁃ing in T-shaped tank for seven days.After that,the behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis.Qualified zebrafish were selected as the blank group.Except for the blank group,zebrafish in the other 5 groups were exposed to AlCl3100μg·L-1 aquaculture water for modeling,and exposed for 6 d.The behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis,and Select the successfully modeled zebraf⁃ish.After that,huperzine A(4μg·L-1)and Huan⁃glian Jiedu decoction of low,medium and high doses(154,308 and 616 mg·L-1)were adminis⁃tered respectively,and exposed for six days.Then,the behavior analysis was conducted again through the behavioral record analysis soft⁃ware Smart 3.0 to select qualified zebrafish.After the training,the brain and gut of zebrafish in each group were collected,and the expression changes of N-cadherin,p-P38/p38MAPK and p-Tau in the brain were detected by Western blot⁃ting and qPCR to show the effect of Huanglian Jiedu decoction on cognitive dysfunction of Zebrafish with Alzheimer disease.RESULTS Western blotting and qPCR results showed that the contents of N-cadherin increased(P<0.05),and the contents of p-P38/p38MAPK and p-Tau decreased(P<0.05)compared with the model group,indicating that Huanglian Jiadu decoction had an effect on the cognitive dysfunction of zebrafish with Alzheimer disease.CONCLU⁃SION Huanglian Jiedu decoction can alleviate cognitive dysfunction of zebrafish model with Alzheimer disease to a certain extent.
文摘Objective:To assess the correlation of signs of myocardial damage to serum cardiac troponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated neonates and 25 controls at 12 h of age by immunoassay.The asphyxiated neonates were followed up until discharge or death.Results:Asphyxiated neonates had significantly higher concentrations of cTnI and CK-MB than controls(P<0.001).Serum cTnI concentrations were significantly higher in asphyxiated neonates who developed hypotension,heart failure or those had low ejection fraction(P<0.01).Serum cTnI concentrations were significantly higher in asphyxiated who died than those who survived(P<0.01).There was no significant difference in serum CK-MB mass concentrations between asphyxiated neonates with and without these complications.Conclusion:Unlike CK-MB,serum cTnI concentrations are significantly higher in asphyxiated neonates who died or developed cardiac dysfunction.
文摘Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.
文摘Current pharmacological therapies used in clinical practice for individuals with cardiac, hepatic, renal or pulmonary fibrosis do not show desirable effects; therefore, new targets of therapy are urgently required. Mitochon- dria play pivotal role in energy production, metabolism, serving as storage tanks of calcium ions and cell fate deter- mination. Recent results of our experiments and other authors＇ studies suggest that the electron transport chain dys- function, electron leakage increasing, the accumulation of fragmented mitochondria, and the impairment in the mi- tophagy system contribute to pathogenesis of tissue fibrosis. Mitochondria targeting compounds exert promise in trea- ring and attenuating the progress of these diseases, indicating potential strategies to target mitochondria in the treat- ment of tissue fibrosis.
基金Natural Science Foundation of Tibet Autonomous Region(2015ZR-13-16)。
文摘OBJECTIVE To evaluate the effects of flavonoids from Xindakang(Hippophae Fructus flavone)on myocardial systolic and diastolic functions of isolated frog hearts and explore the possible mechanism,and provide experimental basis for improving the effect and efficacy of Xindakang on cardiac function.METHODS The isolated frog heart perfusion specimens were prepared by Yagi′s method,and the effects of different concentrations of Xindakang on myocardial contractility(0.0125,0.025,0.05,0.1 and 0.2 g·L^(-1)),heart rate and cardiac output of isolated frog heart were studied.Acetylcholine,atropine and epinephrine were administered successively to analyze the effects of Xindakang on cardiac systolic function of isolated frogs under the action of different drugs,and compared with propranolol.The effect of extracellular calcium ion concentration on the action of Xindakang was studied by using low calcium concentration,high calcium concentration and normal Ren′s solution.To study the effect and possible mechanism of Xindakang on cardiac systolic function of frog.RESULTS The concentration of Xindakang in the range of 0.0125-0.1 g·L^(-1)could weaken the contractility of isolated frog heart and increase the concentration of Xindakang.The inhibitory effect of Xindakang on contractility of isolated frog heart was enhanced,and showed obvious dose-effect relationship.Cardiac output was significantly decreased by Xindakang(P<0.01),slow heart rate(P<0.05);M receptor blocker atropine could not antagonize the contractile effect of Xindakang,and Xindakang could not completely antagonize the contractile effect of adrenalin.Xindakang could inhibit the isolated frog heart in low calcium concentration,high calcium concentration and normal Ren′s solution,and increased with the increase of extracellular calcium concentration(P<0.01).CONCLUSION Xindakang has inhibitory effect on isolated frog heart,which may be achieved by blocking the calcium channel on myocardial cell membrane and reducing the calcium concentration in myocardial cells.
文摘Aim As we all know, apelin acts as the endogenous ligand of APJ, being a member of G protein cou- pled receptors family, apelin/APJ system is involved in plentiful diseases and extremely responsible for the occur- rence and the development of cardiovascular diseases, among many kinds of heart diseases, it is the cardiac hyper- trophy that catches our attention. The myocardial expression of apelin/APJ decreased in rats with left ventrieular hypertrophy suggesting us there is a link between apelin and cardiac hypertrophy. Furthermore, it has been repor- ted that apelin is able to alleviate cardiac hypertrophy induced by Ang II, H202 and exercise. Nevertheless, our la- boratory discovered that apelin is certain to induce cardiac hypertrophy through PI3k-Akt-ERK1/2-p70S6K pathway or via up-regulating the levels of ROS to cause oxidative stress. The above-mentioned contradiction indicates us apelin may have dual effects in cardiac hypertrophy. Moreover, we also illuminate that apelin is involved in some diseases such as obesity, diabetes, hypertension, myoearditis and myocardial infarction, eoineidentally, all these diseases are associated with cardiac hypertrophy. Therefore, this review is aim to unveil the intricate relationship between apelin and cardiac hypertrophy.
文摘Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely associated with cognitive impairment.Therefore,this research aimed to explore whether the HMGB1/TLR4 pathway involves in chronic stress-induced cognitive dysfunction.Methods The chronic unpredictable mild stress(CUMS)mouse model was established by randomly giving different types of stress every day for four consecutive weeks.Cognitive function was detected by novel object recognition test,Y-maze test,and Morris water maze test.The protein expressions of HMGB1,TLR4,B-cell lymphoma 2(BCL2),and BCL2 associated X(BAX)were determined by Western blot.The damage of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin(HE)staining.Results The protein expressions of HMGB1 and TLR4 were significantly increased in the hippocampus of chronic stress mice.Furthermore,inhibition of the HMGB1/TLR4 pathway induced by ethyl pyruvate(EP,a specific inhibitor of HMGB1)and TAK242(a selective inhibitor of TLR4)treatment attenuated cognitive impairment in chronic stress mice,according to the novel object recognition test,Y-maze test,and Morris water maze test.In addition,administration of EP and TAK242 also mitigated the increase of apoptosis in the hippocampus of chronic stress mice.Conclusion These results indicate that the hippocampal HMGB1/TLR4 pathway contributes to chronic stress-induced apoptosis and cognitive dysfunction.
