BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture...BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.展开更多
The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is ...The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.展开更多
Ovotransferrin,an iron-binding glycoprotein,accounting for approximately 12%of egg white protein,is a member of transferrin fam ily.Our previous studies showed that ovotransferrin stimulates the proliferation and diff...Ovotransferrin,an iron-binding glycoprotein,accounting for approximately 12%of egg white protein,is a member of transferrin fam ily.Our previous studies showed that ovotransferrin stimulates the proliferation and differentiation of osteoblasts,while inhibits osteoclastogenesis and resorption activity.The work aims to study the efficacy of orally administered ovotransferrin on the prevention of osteoporosis using ovariectomized(OVX)Sprague-Dawley rats.Oral administration of ovotransferrin showed no negative effect on body weight,food intake and organ weight.After 12-week treatment,feeding ovotransferrin at a dose of 1%(1 g ovotransferrin/100 g diet)prevented OVX-induced bone loss and maintained relatively high bone mineral density and integrated bone microarchitecture.The serum concentration of biomarkers indicating bone formation was increased in ovotransferrin administration groups,while the bone resorption biomarkers were decreased.Ovotransferrin feeding also decreased the production of serum cytokine TNF-αand IL-6,which are two stimulators for osteoclast differentiation.In addition to its direct regulatory role on bone turnover,ovotransferrin supplementation might benefit osteoporosis prevention by inhibiting adipogenesis,and regulating immune response.Our results suggested the potential application of ovotransferrin as a functional food ingredient on the prevention of osteoporosis.展开更多
Mitochondria were isolated from normal and cold adapted rat livers.The respiratory func-tion of mitochondria in rat livers,including ADP:O ratio(P/O)and the respiratory control ratio(RCR),was determined by oxygen elec...Mitochondria were isolated from normal and cold adapted rat livers.The respiratory func-tion of mitochondria in rat livers,including ADP:O ratio(P/O)and the respiratory control ratio(RCR),was determined by oxygen electrode method,The protein synthesis in mitochondria wasstudied by observing the incorporation of[~3H]-Leucine into mitochondria.Polyacrylamide gelelectrophoresis was carried out to detect the changes of the inner membrane proteins.It was shownthat the P/O and RCR decreased in cold adapted rats in the 2nd and 4th weeks and returned tothe control level in the 6th week,the protein synthesis of mitochondria decreased significantly incold adapted rats in 1,2 and 4 weeks;the electrophoretic pattern of the inner membrane proteinsin mitochondria from cold adapted rat livers revealed some new bands.展开更多
Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine ...Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.展开更多
This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. ...This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. Ranitidine (R) 0.03% in the diet, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)50 μg/ml in drinking water, or both of them were administered to Wistar rats for 20 weeks. The iats were maintained without the drugs for additional 23 weeks. A control group of rats without any treatment of drugs were kept for 43 weeks Intestinal metaplasia (IM) was found in 86.5% of the rats in MNNG group, 22.5% in R groupand 100% in MNNG+R while only 7.5% in the control. The incidence of IM was significantly different between MNNG+R group and R group or MNNG group. The number of metaplastic glands was also the highest in the MNNG+R group. The therapeutic effects of retinoic acid (RA) and sodium butyrate (SB) on the iNduced precancerousous lesions of the glandular gastric mucosa were observed. It was found that the incidence of IM, moderate and severe dysplasia, and gastric cancer and the number of metaplastic glands in the pylorus and fundus were significantly lower in RA treated group (72.0%, 24.0%, 0%, 130.2±93.9 and 51.5±39.1) and SB treated gioup (60.0%,20.0%, 0%, 70.3±46.8, and 39.8±29.6) than in the RA untreated group (100%, 52.2%, 16.0%, 442.4±230.0 and 247.4±112.07) and the SB untreated group (88.0%, 48.0%. 16.0%, 241.4±113.9 and 146.4±66.3)(P<0.01 to 0.05). A mucosal flap with vascular pedicle from the gastric wall of the Wistar rats was transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3td, 6th, 9th and 12th month after operation. IM was found in all the gastric grafts to the intestines with optical and electron microscopy. It is concluded on the basis of the findings that the concomitant administration of MNNG and R is a reliable method to induce IM of gastric mucosa in rats; RA and SB are efficient agents for the reverse thevapy of the precancerous lesions of gastric glandular mucosa in rats; and the formation of IM of gastric mucosa might be a pH-related process. The possible mechanism of the development of IM was discussed.展开更多
BACKGROUND： Paraquat （PQ） intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative s...BACKGROUND： Paraquat （PQ） intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative stress damage. This study aimed to investigate the protective effects and the possible mechanisms of intoxication on rats with acute lung injury （ALl） caused by paraquat poisoning. METHODS： Thirty PQ poisoned rats were randomly divided into a PQ intoxication group （intoxication group）, a saturated hydrogen saline intervention group （intervention group）, and a control group, with 10 rats in each group. The first two groups accepted an intragastric administration of PQ at a dose of 50 mg/kg for every single rat, and the control group was fed with a same volume of normal saline. Five mL/kg of saturated hydrogen saline was given to the intervention group three times a day by peritoneal injection for three days after intoxication. Arterial blood gas was detected on the third day. The rats were executed and their lungs were taken for measurement of wet dry weight ratio, homogenate malondialdehyde （MDA）, and 8-hydroxy-2＇-deoxyguanosine （8-OhdG）. Histological changes of the lungs were also observed. RESULTS： Compared with the control group, the intoxication group had more serious hypoxemia, greater wet/dry weight ratio, higher MDA level, higher expression of 8-OhdG and more severe lung damage （P〈0.01 or P〈0.05）. However, after intervention with saturated hydrogen saline, poisoned animals turned to have lighter hypoxemia, smaller wet/dry weight ratio, lower MDA level, lower expression of 8-OhdG, and milder lung damage （P〈0.01 or P〈0.05）. CONCLUSIONS： Saturated hydrogen sal by PQ. Possibly, it can neutralize toxic oxygen injury induced by PQ. ne is effective in preventing acute lung injury caused radicals selectively and alleviate the oxidative stress展开更多
Objective:To study the time-course of the regeneration of GAP-43+ nerve, and the effects of NGF and TrkA on this process. Methods: Adult Wistar rats underwent splenectomy and splenic autotransplantation, or sham-opera...Objective:To study the time-course of the regeneration of GAP-43+ nerve, and the effects of NGF and TrkA on this process. Methods: Adult Wistar rats underwent splenectomy and splenic autotransplantation, or sham-operation. On day 7, 14, 30, 60, 90, 120, and 180 after surgery, the density of GAP-43+ nerve fibers in spleen tissues were measured with the immunohistochemistry followed by computer image analysis. The expressions of GAP-43, NGF and TrkA were determined with in situ hybrdization, and their mRNA levels were detected with RT-PCR and image analysis qualification. Results: (1) The GAP-43+ nerve fibers began their regeneration on 30 d after operation and extended from greater omentum into splenic autotransplants. Density of the nerve fibers gradually became greater and almost normal 180 d after operation. (2) In splenic autografts, the mRNA expression of GAP-43, NGF and TrkA appeared on day 30 after the operation, gradually reached the peak on day 90. Conclusion: The renascent GAP-43+ nerve fibers may come from the greater omentum packaging the splenic autografts and NGF and TrkA can promote the nerval regeneration in the autotransplant spleen tissues.展开更多
Hydroxylammonium nitrate(HAN) is a major constituent in a class of liquid monopropellants and is extensively used in nuclear industry and space propulsion.Previous toxicological studies have focused on oral,inhalation...Hydroxylammonium nitrate(HAN) is a major constituent in a class of liquid monopropellants and is extensively used in nuclear industry and space propulsion.Previous toxicological studies have focused on oral,inhalation and dermal routes of exposure to HAN-based propellant blends.In this study,acute and subchronic toxicity of HAN in Wistar rats by intraperitoneal injections were evaluated.In this acute study,doses of HAN at 115,125,135,147,160 or 174 mg/kg were administered.No adverse effects were observed during a 14-day period and at gross histopathological examination.In the subchronic study,HAN at 7,14 or 28 mg/kg were administered for 13 weeks.The treatment with HAN caused significant changes in the weight of spleen,in the level of hematological parameters,total bilirubin,direct bilirubin,uric acid and carbondioxidecombining power and histopathological damages of the lung,liver,spleen and kidney.Overall,the study suggests that 13-week HAN treatment caused abnormal hematological changes and tissue lesions,and the risk of toxicity to mammals is not negligible.展开更多
Polyunsaturated fatty acids(PUFAs),particularly the omega-3 PUFAs,are thought to be involved in neuronal processes,to play a role in neurodevelopmental disorders and to be important for the integrity of central nervou...Polyunsaturated fatty acids(PUFAs),particularly the omega-3 PUFAs,are thought to be involved in neuronal processes,to play a role in neurodevelopmental disorders and to be important for the integrity of central nervous system functioning.The present study investigated the effects of nutritional omega-3 PUFAs on attentional functions and impulsive behavior in Wistar rats.For this purpose,female Wistar rats were fed an omega-3 deficient diet over several generations,and the dams of the seventh generation were randomly assigned to two diet groups and fed an omega-3 deficient or an omega-3 sufficient diet.In addition,a group of previously untreated dams was fed an omega-3 sufficient diet.The male offspring of these three diet groups were tested using an established paradigm for the assessment of attention and impulsive behavior,i.e.a modified version of the five-choice-serial-reaction-time task(5CSRTT).The present data show that the deficiency of omega-3 PUFAs over generations led to substantial changes in attentional processes and impulsive behaviors.The impairments associated with an omega-3 deficiency were partly corrected by treatment with the omega-3 sufficient diet in the last generation of the omega-3 deficient group which showed substantial improvements in attention parameters.While there were no significant effects of dietary modifications on psychomotor activity levels,there was some evidence for changes in impulsive behavior.In conclusion,transgenerational dietary changes in the availability of omega-3 PUFAs led to changes in attentional processes and impulsive behavior in rats,supporting the hypothesis that omega-3 PUFAs play a role in cognitive and behavioral processes.The present findings offer a promising approach in the investigation of the role of omega-3 PUFAs in a variety of cognitive and behavioral domains.展开更多
Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ failure.Materials and methods The experimental model of multiple organ failure was made in adult and old rats by h...Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ failure.Materials and methods The experimental model of multiple organ failure was made in adult and old rats by hypoperfusion-induced hemorrhagic shock. After blood sampling, the arterial acetoacetate, β-hydroxybutyrate, total ketone body, ALT, AST, BUN, creatinine at 2, 4, 8 hr in hypoperfusion were examined to compare the differences of ketone body ratio and organ failure between adult and old rats. Hepatic and mitochondrial metabolism were assessed by comparing ketone body ratios (AcAc/β-OHB) and free NAD+/NADH ratios. Results Ketone body ratio in old rats at 2, 4, 8 hr after the induction of hemorrhagic shock decreased from 0.68 to 0.31, 0.27 and 0.22, respectively. In adult rats, it decreased from 1.12 to 0.17, 0.12 and 0.09, respectively. Changes of ketone body ratio in the adult group were larger than in the elderly group ( P ＜ 0.001). The development of multiple organ failure is associated with the time of hemorrhagic shock development. Conclusions There was a different ketone body ratio between multiple organ failure in the elderly (MOFE) and multiple organ failure (MOF) in general adults. Ketone body ratio is a better indicator than ALT and AST in reflecting hepatic function in the early status of MOF. (J Geriatr Cardiol 2004;1(2) :125-128. )展开更多
Swertisin contents in rat urine,feces and tissues were determined by reversed-phase high-performance liquid chromatography（RP-HPLC） method.Chromatographic separations were performed on a C18 column with acetonitrile...Swertisin contents in rat urine,feces and tissues were determined by reversed-phase high-performance liquid chromatography（RP-HPLC） method.Chromatographic separations were performed on a C18 column with acetonitrile-water（23：77,v/v） as the mobile phase.The calibration curves were linear over the ranges of 0.175-35.0μg/mL for rat urine,0.5-60.0μg/mL for rat feces,and 0.014 to 53.0μg/mL for all tissues.The inter-and intra-day precisions and accuracy for all measured samples were satisfactory.The fully validated method was applied for tissue distribution and excretion of swertisin in rat urine and bile after intravenous administration.The maximum level of swertisin was found in kidney,which reached 83.87± 6.36μg/g.In rat heart,swertisin was hardly detected under used experimental conditions.Swetisin level in liver,kidney,stomach,smooth muscle and skeletal muscle continued to decrease from 5 to 60min.Swertisin showed increasing tendency in intestine,spleen and testis tissues at scheduled time points.Detectable swertisin was found in brain and lung tissue.Totally 11.9% swertisin dose was cumulatively excreted from urine in 60h after intravenous administration.There was small amount of swertisin in rat feces and the cumulative excretion level reached 4.59% of intravenous dose in 60h.展开更多
Microinjection of 0.5μg guanabenz(GB)into the nucleus tractus solitarii(NTS)orintravenous(i.v.)injection of 10μg/kg of GB significantly lowered plasma renin activity(PRA).blood pressure(BP)and heart rate(HR)in rats ...Microinjection of 0.5μg guanabenz(GB)into the nucleus tractus solitarii(NTS)orintravenous(i.v.)injection of 10μg/kg of GB significantly lowered plasma renin activity(PRA).blood pressure(BP)and heart rate(HR)in rats i.v.10 μg/kg GB,after the bilateral NIS were de-stroyed by electric current(1 mA 20s),did not decrease PRA,BP and HR.These findings suggestthat the inhibitory action of GB on PRA,BP and HR is related to the activation of alpha-2adrenoceptors in the NTS.展开更多
We tried to clarify the role of oxygen radicals released from granulocytes stimulated byphorbol myristate acetate(PMA) in rat acute lung injury. It was found that DNA strand-breakdamage(DSBD) in peripheral white blood...We tried to clarify the role of oxygen radicals released from granulocytes stimulated byphorbol myristate acetate(PMA) in rat acute lung injury. It was found that DNA strand-breakdamage(DSBD) in peripheral white blood cells (WBC) was significantly increased 40 min after injec-tion of PMA. DSBD in lung tissue of rats treated with PMA was also markedly increased comparedwith the controls. The PMA-treated rats showed significantly higher lipid-peroxide (LPO) level inplasma and lung tissue hemogenate than the controls did. These results suggest that determination ofDSBD, a simple and sensitive indicator for oxygen radical damaging, might be useful in thediagnosis of adult respiratory distress syndrome (ARDS), when it is used together with themeasurement of plasma LPO.展开更多
Background:After renal trauma,surgical treatment is vital,but sometimes there may be loss of function due to fibrosis.This study aimed to evaluate the effect of autologous omentum flaps on injured renal tissues in a r...Background:After renal trauma,surgical treatment is vital,but sometimes there may be loss of function due to fibrosis.This study aimed to evaluate the effect of autologous omentum flaps on injured renal tissues in a rat model.Methods:A total of 30 Wistar albino rats were included and randomly divided equally into a control group and four intervention groups.Iatrogenic renal injuries were repaired using a surgical technique(primary repair 1 group and primary repair 2 group)or transposition of the autologous omentum(omentum repair 1 group and omentum repair 2 group).Blood samples were taken preoperatively and on the 1st and 7th postoperative days in all groups and on the 18th postoperative day in the control and two intervention groups.All rats were sacrificed on the 7th or 18th day postoperatively,and their right kidneys were taken for histopathological evaluation.Results:The mean urea level significantly decreased from day 1 to day 7 and from day 1 to day 18 in the omentum repair 2 group(P=0.005 and P=0.004,respectively).There were no other significant changes in urea or creatinine levels within the intervention groups(P>0.05).There was no significant correlation between the urea and creatinine levels and the histological scores(P>0.05).The primary repair 1 and 2 groups had significantly higher median granulation and inflammation scores in the kidney specimen than the control and omentum repair groups(P<0.05).The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group(P<0.05).The completion score for the healing process in the kidney specimen was significantly higher in the omentum repair groups than in the primary repair groups(P<0.05).The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group(P<0.05).Granulation degree in the kidney specimen was strongly and positively correlated with the inflammation degree(r=0.824,P<0.001)and foreign body reaction in the kidney specimen(r=0.872,P<0.001)and a strong and negative correlation with the healing process completion score in the kidney(r=−0.627,P=0.001).Inflammation degree in the kidney specimen was strongly and positively correlated with the foreign body reaction in the kidney specimen(r=0.731,P=0.001)and strongly and negatively correlated with the healing process completion score in the kidney specimen(r=−0.608,P=0.002).Conclusion:Autologous omentum tissue for kidney injury repair attenuated inflammation and granulation.Additionally,the use of omental tissue to facilitate healing of kidney injury may theoretically lead to a more effective healing process and reduced fibrosis and tissue and function loss.展开更多
Following extensive bowel resection, the intestinal tract undergoes a variety of adaptive responses to enhance bowel function. The purpose of this study was to determine the effect of glutamine-supplemented parenteral...Following extensive bowel resection, the intestinal tract undergoes a variety of adaptive responses to enhance bowel function. The purpose of this study was to determine the effect of glutamine-supplemented parenteral nutrition on mucosal cellularity and gut function. In addition, enterocyte gene expression of two relevant systems was also characterized and related to the structural and functional changes that occurred. Male Wistar rats underwent a 60% small bowel resection and jugular vein catheterization and were randomized into two groups. The control group (n = 10) received a standard intravenous nutritional solution and the study group (n = 10) received a similar solution but enriched with alanylglutamine dipeptide. After 7 days blood was taken for amino acid analysis, and bowel was harvested to determine mucosal morphology and expression of mucosal cell glutaminase and IGF-I mRNA. Mesentery lymphnodes were cultured to determine the presence of bacteria and thus access bacteria translocation. Serum glutamine concentration and mucosal architecture were maintained in the study group compared to the controls. Seventy percent of lymphnodes were cultured positive in control vs. only 20% in the study group (P展开更多
Objective: To screen the differentially expressed gene in liver regeneration with cDNA array and gain insight of the pathogenesis of the acute hepatic failure. Methods: Acute liver failure model in Sprague-Dawley (SD)...Objective: To screen the differentially expressed gene in liver regeneration with cDNA array and gain insight of the pathogenesis of the acute hepatic failure. Methods: Acute liver failure model in Sprague-Dawley (SD) rat was induced by 95% hepatectomy. The differential expression profiles in regenerating rat liver were studied by a cDNA array representing 1176 cDNA clusters. Some genes were randomly selected from a pool of differentially expressed genes and subjected to RT-PCR to further confirm the result from microarray hybridization. Results: The alterations of transcription levels were noted in the expressions of 188 genes. There were 138 genes with their expression up-regulated such as growth factors, PCNA, ribosomal proteins, IL6 and CDKs which were associated with cell cycle regulation, stress, metabolism and proliferation. Conclusion: cDNA array is a powerful tool to explore the gene expression of acute liver failure and is potential for the diagnosis and treatment of liver regeneration.展开更多
基金supported by a grant from National Natural Science Foundation of China (82272196)。
文摘BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.
基金supported by the National Natural Science Foundation of China(No.31901635)。
文摘The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.
基金funded by grants from Egg Farmers of Canada,Global Egg Corp.,and Natural Sciences and Engineering Research Council of Canada(NSERC)。
文摘Ovotransferrin,an iron-binding glycoprotein,accounting for approximately 12%of egg white protein,is a member of transferrin fam ily.Our previous studies showed that ovotransferrin stimulates the proliferation and differentiation of osteoblasts,while inhibits osteoclastogenesis and resorption activity.The work aims to study the efficacy of orally administered ovotransferrin on the prevention of osteoporosis using ovariectomized(OVX)Sprague-Dawley rats.Oral administration of ovotransferrin showed no negative effect on body weight,food intake and organ weight.After 12-week treatment,feeding ovotransferrin at a dose of 1%(1 g ovotransferrin/100 g diet)prevented OVX-induced bone loss and maintained relatively high bone mineral density and integrated bone microarchitecture.The serum concentration of biomarkers indicating bone formation was increased in ovotransferrin administration groups,while the bone resorption biomarkers were decreased.Ovotransferrin feeding also decreased the production of serum cytokine TNF-αand IL-6,which are two stimulators for osteoclast differentiation.In addition to its direct regulatory role on bone turnover,ovotransferrin supplementation might benefit osteoporosis prevention by inhibiting adipogenesis,and regulating immune response.Our results suggested the potential application of ovotransferrin as a functional food ingredient on the prevention of osteoporosis.
文摘Mitochondria were isolated from normal and cold adapted rat livers.The respiratory func-tion of mitochondria in rat livers,including ADP:O ratio(P/O)and the respiratory control ratio(RCR),was determined by oxygen electrode method,The protein synthesis in mitochondria wasstudied by observing the incorporation of[~3H]-Leucine into mitochondria.Polyacrylamide gelelectrophoresis was carried out to detect the changes of the inner membrane proteins.It was shownthat the P/O and RCR decreased in cold adapted rats in the 2nd and 4th weeks and returned tothe control level in the 6th week,the protein synthesis of mitochondria decreased significantly incold adapted rats in 1,2 and 4 weeks;the electrophoretic pattern of the inner membrane proteinsin mitochondria from cold adapted rat livers revealed some new bands.
文摘Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.
文摘This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. Ranitidine (R) 0.03% in the diet, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)50 μg/ml in drinking water, or both of them were administered to Wistar rats for 20 weeks. The iats were maintained without the drugs for additional 23 weeks. A control group of rats without any treatment of drugs were kept for 43 weeks Intestinal metaplasia (IM) was found in 86.5% of the rats in MNNG group, 22.5% in R groupand 100% in MNNG+R while only 7.5% in the control. The incidence of IM was significantly different between MNNG+R group and R group or MNNG group. The number of metaplastic glands was also the highest in the MNNG+R group. The therapeutic effects of retinoic acid (RA) and sodium butyrate (SB) on the iNduced precancerousous lesions of the glandular gastric mucosa were observed. It was found that the incidence of IM, moderate and severe dysplasia, and gastric cancer and the number of metaplastic glands in the pylorus and fundus were significantly lower in RA treated group (72.0%, 24.0%, 0%, 130.2±93.9 and 51.5±39.1) and SB treated gioup (60.0%,20.0%, 0%, 70.3±46.8, and 39.8±29.6) than in the RA untreated group (100%, 52.2%, 16.0%, 442.4±230.0 and 247.4±112.07) and the SB untreated group (88.0%, 48.0%. 16.0%, 241.4±113.9 and 146.4±66.3)(P<0.01 to 0.05). A mucosal flap with vascular pedicle from the gastric wall of the Wistar rats was transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3td, 6th, 9th and 12th month after operation. IM was found in all the gastric grafts to the intestines with optical and electron microscopy. It is concluded on the basis of the findings that the concomitant administration of MNNG and R is a reliable method to induce IM of gastric mucosa in rats; RA and SB are efficient agents for the reverse thevapy of the precancerous lesions of gastric glandular mucosa in rats; and the formation of IM of gastric mucosa might be a pH-related process. The possible mechanism of the development of IM was discussed.
文摘BACKGROUND： Paraquat （PQ） intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative stress damage. This study aimed to investigate the protective effects and the possible mechanisms of intoxication on rats with acute lung injury （ALl） caused by paraquat poisoning. METHODS： Thirty PQ poisoned rats were randomly divided into a PQ intoxication group （intoxication group）, a saturated hydrogen saline intervention group （intervention group）, and a control group, with 10 rats in each group. The first two groups accepted an intragastric administration of PQ at a dose of 50 mg/kg for every single rat, and the control group was fed with a same volume of normal saline. Five mL/kg of saturated hydrogen saline was given to the intervention group three times a day by peritoneal injection for three days after intoxication. Arterial blood gas was detected on the third day. The rats were executed and their lungs were taken for measurement of wet dry weight ratio, homogenate malondialdehyde （MDA）, and 8-hydroxy-2＇-deoxyguanosine （8-OhdG）. Histological changes of the lungs were also observed. RESULTS： Compared with the control group, the intoxication group had more serious hypoxemia, greater wet/dry weight ratio, higher MDA level, higher expression of 8-OhdG and more severe lung damage （P〈0.01 or P〈0.05）. However, after intervention with saturated hydrogen saline, poisoned animals turned to have lighter hypoxemia, smaller wet/dry weight ratio, lower MDA level, lower expression of 8-OhdG, and milder lung damage （P〈0.01 or P〈0.05）. CONCLUSIONS： Saturated hydrogen sal by PQ. Possibly, it can neutralize toxic oxygen injury induced by PQ. ne is effective in preventing acute lung injury caused radicals selectively and alleviate the oxidative stress
文摘Objective:To study the time-course of the regeneration of GAP-43+ nerve, and the effects of NGF and TrkA on this process. Methods: Adult Wistar rats underwent splenectomy and splenic autotransplantation, or sham-operation. On day 7, 14, 30, 60, 90, 120, and 180 after surgery, the density of GAP-43+ nerve fibers in spleen tissues were measured with the immunohistochemistry followed by computer image analysis. The expressions of GAP-43, NGF and TrkA were determined with in situ hybrdization, and their mRNA levels were detected with RT-PCR and image analysis qualification. Results: (1) The GAP-43+ nerve fibers began their regeneration on 30 d after operation and extended from greater omentum into splenic autotransplants. Density of the nerve fibers gradually became greater and almost normal 180 d after operation. (2) In splenic autografts, the mRNA expression of GAP-43, NGF and TrkA appeared on day 30 after the operation, gradually reached the peak on day 90. Conclusion: The renascent GAP-43+ nerve fibers may come from the greater omentum packaging the splenic autografts and NGF and TrkA can promote the nerval regeneration in the autotransplant spleen tissues.
基金the Scientific Research Foundation for Medica Science and Public Health of PLA (06z032)
文摘Hydroxylammonium nitrate(HAN) is a major constituent in a class of liquid monopropellants and is extensively used in nuclear industry and space propulsion.Previous toxicological studies have focused on oral,inhalation and dermal routes of exposure to HAN-based propellant blends.In this study,acute and subchronic toxicity of HAN in Wistar rats by intraperitoneal injections were evaluated.In this acute study,doses of HAN at 115,125,135,147,160 or 174 mg/kg were administered.No adverse effects were observed during a 14-day period and at gross histopathological examination.In the subchronic study,HAN at 7,14 or 28 mg/kg were administered for 13 weeks.The treatment with HAN caused significant changes in the weight of spleen,in the level of hematological parameters,total bilirubin,direct bilirubin,uric acid and carbondioxidecombining power and histopathological damages of the lung,liver,spleen and kidney.Overall,the study suggests that 13-week HAN treatment caused abnormal hematological changes and tissue lesions,and the risk of toxicity to mammals is not negligible.
文摘Polyunsaturated fatty acids(PUFAs),particularly the omega-3 PUFAs,are thought to be involved in neuronal processes,to play a role in neurodevelopmental disorders and to be important for the integrity of central nervous system functioning.The present study investigated the effects of nutritional omega-3 PUFAs on attentional functions and impulsive behavior in Wistar rats.For this purpose,female Wistar rats were fed an omega-3 deficient diet over several generations,and the dams of the seventh generation were randomly assigned to two diet groups and fed an omega-3 deficient or an omega-3 sufficient diet.In addition,a group of previously untreated dams was fed an omega-3 sufficient diet.The male offspring of these three diet groups were tested using an established paradigm for the assessment of attention and impulsive behavior,i.e.a modified version of the five-choice-serial-reaction-time task(5CSRTT).The present data show that the deficiency of omega-3 PUFAs over generations led to substantial changes in attentional processes and impulsive behaviors.The impairments associated with an omega-3 deficiency were partly corrected by treatment with the omega-3 sufficient diet in the last generation of the omega-3 deficient group which showed substantial improvements in attention parameters.While there were no significant effects of dietary modifications on psychomotor activity levels,there was some evidence for changes in impulsive behavior.In conclusion,transgenerational dietary changes in the availability of omega-3 PUFAs led to changes in attentional processes and impulsive behavior in rats,supporting the hypothesis that omega-3 PUFAs play a role in cognitive and behavioral processes.The present findings offer a promising approach in the investigation of the role of omega-3 PUFAs in a variety of cognitive and behavioral domains.
文摘Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ failure.Materials and methods The experimental model of multiple organ failure was made in adult and old rats by hypoperfusion-induced hemorrhagic shock. After blood sampling, the arterial acetoacetate, β-hydroxybutyrate, total ketone body, ALT, AST, BUN, creatinine at 2, 4, 8 hr in hypoperfusion were examined to compare the differences of ketone body ratio and organ failure between adult and old rats. Hepatic and mitochondrial metabolism were assessed by comparing ketone body ratios (AcAc/β-OHB) and free NAD+/NADH ratios. Results Ketone body ratio in old rats at 2, 4, 8 hr after the induction of hemorrhagic shock decreased from 0.68 to 0.31, 0.27 and 0.22, respectively. In adult rats, it decreased from 1.12 to 0.17, 0.12 and 0.09, respectively. Changes of ketone body ratio in the adult group were larger than in the elderly group ( P ＜ 0.001). The development of multiple organ failure is associated with the time of hemorrhagic shock development. Conclusions There was a different ketone body ratio between multiple organ failure in the elderly (MOFE) and multiple organ failure (MOF) in general adults. Ketone body ratio is a better indicator than ALT and AST in reflecting hepatic function in the early status of MOF. (J Geriatr Cardiol 2004;1(2) :125-128. )
基金Supported by the Excellent Young Scholars Research Foundation of Beijing Institute of Technology(2007Y0612)
文摘Swertisin contents in rat urine,feces and tissues were determined by reversed-phase high-performance liquid chromatography（RP-HPLC） method.Chromatographic separations were performed on a C18 column with acetonitrile-water（23：77,v/v） as the mobile phase.The calibration curves were linear over the ranges of 0.175-35.0μg/mL for rat urine,0.5-60.0μg/mL for rat feces,and 0.014 to 53.0μg/mL for all tissues.The inter-and intra-day precisions and accuracy for all measured samples were satisfactory.The fully validated method was applied for tissue distribution and excretion of swertisin in rat urine and bile after intravenous administration.The maximum level of swertisin was found in kidney,which reached 83.87± 6.36μg/g.In rat heart,swertisin was hardly detected under used experimental conditions.Swetisin level in liver,kidney,stomach,smooth muscle and skeletal muscle continued to decrease from 5 to 60min.Swertisin showed increasing tendency in intestine,spleen and testis tissues at scheduled time points.Detectable swertisin was found in brain and lung tissue.Totally 11.9% swertisin dose was cumulatively excreted from urine in 60h after intravenous administration.There was small amount of swertisin in rat feces and the cumulative excretion level reached 4.59% of intravenous dose in 60h.
文摘Microinjection of 0.5μg guanabenz(GB)into the nucleus tractus solitarii(NTS)orintravenous(i.v.)injection of 10μg/kg of GB significantly lowered plasma renin activity(PRA).blood pressure(BP)and heart rate(HR)in rats i.v.10 μg/kg GB,after the bilateral NIS were de-stroyed by electric current(1 mA 20s),did not decrease PRA,BP and HR.These findings suggestthat the inhibitory action of GB on PRA,BP and HR is related to the activation of alpha-2adrenoceptors in the NTS.
文摘We tried to clarify the role of oxygen radicals released from granulocytes stimulated byphorbol myristate acetate(PMA) in rat acute lung injury. It was found that DNA strand-breakdamage(DSBD) in peripheral white blood cells (WBC) was significantly increased 40 min after injec-tion of PMA. DSBD in lung tissue of rats treated with PMA was also markedly increased comparedwith the controls. The PMA-treated rats showed significantly higher lipid-peroxide (LPO) level inplasma and lung tissue hemogenate than the controls did. These results suggest that determination ofDSBD, a simple and sensitive indicator for oxygen radical damaging, might be useful in thediagnosis of adult respiratory distress syndrome (ARDS), when it is used together with themeasurement of plasma LPO.
基金the Acıbadem Mehmet Ali Aydınlar University under Grant 2018-03-05.
文摘Background:After renal trauma,surgical treatment is vital,but sometimes there may be loss of function due to fibrosis.This study aimed to evaluate the effect of autologous omentum flaps on injured renal tissues in a rat model.Methods:A total of 30 Wistar albino rats were included and randomly divided equally into a control group and four intervention groups.Iatrogenic renal injuries were repaired using a surgical technique(primary repair 1 group and primary repair 2 group)or transposition of the autologous omentum(omentum repair 1 group and omentum repair 2 group).Blood samples were taken preoperatively and on the 1st and 7th postoperative days in all groups and on the 18th postoperative day in the control and two intervention groups.All rats were sacrificed on the 7th or 18th day postoperatively,and their right kidneys were taken for histopathological evaluation.Results:The mean urea level significantly decreased from day 1 to day 7 and from day 1 to day 18 in the omentum repair 2 group(P=0.005 and P=0.004,respectively).There were no other significant changes in urea or creatinine levels within the intervention groups(P>0.05).There was no significant correlation between the urea and creatinine levels and the histological scores(P>0.05).The primary repair 1 and 2 groups had significantly higher median granulation and inflammation scores in the kidney specimen than the control and omentum repair groups(P<0.05).The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group(P<0.05).The completion score for the healing process in the kidney specimen was significantly higher in the omentum repair groups than in the primary repair groups(P<0.05).The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group(P<0.05).Granulation degree in the kidney specimen was strongly and positively correlated with the inflammation degree(r=0.824,P<0.001)and foreign body reaction in the kidney specimen(r=0.872,P<0.001)and a strong and negative correlation with the healing process completion score in the kidney(r=−0.627,P=0.001).Inflammation degree in the kidney specimen was strongly and positively correlated with the foreign body reaction in the kidney specimen(r=0.731,P=0.001)and strongly and negatively correlated with the healing process completion score in the kidney specimen(r=−0.608,P=0.002).Conclusion:Autologous omentum tissue for kidney injury repair attenuated inflammation and granulation.Additionally,the use of omental tissue to facilitate healing of kidney injury may theoretically lead to a more effective healing process and reduced fibrosis and tissue and function loss.
文摘Following extensive bowel resection, the intestinal tract undergoes a variety of adaptive responses to enhance bowel function. The purpose of this study was to determine the effect of glutamine-supplemented parenteral nutrition on mucosal cellularity and gut function. In addition, enterocyte gene expression of two relevant systems was also characterized and related to the structural and functional changes that occurred. Male Wistar rats underwent a 60% small bowel resection and jugular vein catheterization and were randomized into two groups. The control group (n = 10) received a standard intravenous nutritional solution and the study group (n = 10) received a similar solution but enriched with alanylglutamine dipeptide. After 7 days blood was taken for amino acid analysis, and bowel was harvested to determine mucosal morphology and expression of mucosal cell glutaminase and IGF-I mRNA. Mesentery lymphnodes were cultured to determine the presence of bacteria and thus access bacteria translocation. Serum glutamine concentration and mucosal architecture were maintained in the study group compared to the controls. Seventy percent of lymphnodes were cultured positive in control vs. only 20% in the study group (P
文摘Objective: To screen the differentially expressed gene in liver regeneration with cDNA array and gain insight of the pathogenesis of the acute hepatic failure. Methods: Acute liver failure model in Sprague-Dawley (SD) rat was induced by 95% hepatectomy. The differential expression profiles in regenerating rat liver were studied by a cDNA array representing 1176 cDNA clusters. Some genes were randomly selected from a pool of differentially expressed genes and subjected to RT-PCR to further confirm the result from microarray hybridization. Results: The alterations of transcription levels were noted in the expressions of 188 genes. There were 138 genes with their expression up-regulated such as growth factors, PCNA, ribosomal proteins, IL6 and CDKs which were associated with cell cycle regulation, stress, metabolism and proliferation. Conclusion: cDNA array is a powerful tool to explore the gene expression of acute liver failure and is potential for the diagnosis and treatment of liver regeneration.
