Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the pre...Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions(1/100 and 1/50, m/V)as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis(lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism(higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis(lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans.展开更多
Background: LncRNA AK044604(regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy(DN). In this study, we sought to explore th...Background: LncRNA AK044604(regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy(DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury.Methods: Diabetic db/db mice received Risa-inhibition adeno-associated virus(AAV) via tail vein injection, and intraperitoneal injection of lithium chloride(LiCl). Blood, urine, and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells(MPCs) were cultured and treated with Risa-inhibition lentivirus(LV), EX-527, and LiCl. MPCs were collected under different stimulations as noted. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blotting analysis, transmission electron microscopy,Periodic Acid-Schiff staining, and immunofluorescence staining.Results: Risa and activated GSK3β were overexpressed, but Sirt1 was downregulated in DN mice and high glucosetreated MPCs(P<0.001, db/m vs. db/db, NG or HM vs. HG), which was correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1(P<0.001, db/m vs. db/db, NG or HM vs. HG). In contrast, Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury, which could be abrogated by EX-527(P<0.001, db/db+Risa-AAV vs. db/db, HG+Risa-LV vs. HG). Furthermore, LiCl treatment could restore GSK3β-mediated autophagy of podocytes(P<0.001, db/db+LiCl vs. db/db, HG+LiCl vs. HG), suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy.Conclusions: Risa could inhibit autophagy by regulating the Sirt1/GSK3β axis, thereby aggravating podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.展开更多
(+)-Catechin(CE)is mainly found in green and black tea and has many biological effects,such as antiinflammatory,anti-cancer,anti-viral effects,protecting human organs,especially the kidney.This study aims to identify ...(+)-Catechin(CE)is mainly found in green and black tea and has many biological effects,such as antiinflammatory,anti-cancer,anti-viral effects,protecting human organs,especially the kidney.This study aims to identify the circRNAs induced by CE in db/db mice and their roles in diabetic nephropathy progression.After the db/db mice were treated with CE,RNA-seq was performed to identify the differentially expressed circRNA and mRNAs.The ceRNA regulatory network was constructed and analyzed using bioinformatics software and public databases(Cytoscape,Clue GO,Mi RWalk,STRING,et al.).Our results revealed that 6 differentially expressed circRNAs are most associated with the cholinergic synapse,neurotrophin signaling pathway,and insulin signaling pathway.Among these,circRNA.5549 and circRNA.4712 might regulate Cd36,Cyp26 b1,C8 a,Cyp2 j13,Grem2 genes through ceRNA regulatory mechanism in the presence of CE treatment.The expanded network of proteins interacting with these 5 genes shows that the TGF-βsignaling pathway,signaling pathways regulating pluripotency of stem cell,fat digestion and absorption,and PPAR signaling pathway was highly enriched.Overall,circRNA.5549 and circRNA.4712 exhibit a promotive function in CE-treated db/db mice,especially in circRNA.5549/miR-29a-5P/Cd36 regulatory network,and this evidence suggest that their ceRNA regulatory network might be a therapeutic target for DN in humans.展开更多
To assess the role of hypertension and family history of hypertensio n in the development of nephropathy in patients with non insulin dependent dia betes mellitus (NIDDM).Methods. A retrospective analysis was done on ...To assess the role of hypertension and family history of hypertensio n in the development of nephropathy in patients with non insulin dependent dia betes mellitus (NIDDM).Methods. A retrospective analysis was done on 2 groups of NIDDM patients, one g roup without proteinuria (urine protein< 300mg/24h, n=106) and the other group w ith proteinuria (urine protein≥500mg/24h, n=106). The 2 groups were matched by age(≤±3yrs), sex, ethnic and resident place. Some information of these subject s including demographic; history of disease, family history of diseases, lifesty le and behavior style variables was obtained by questionnaire; some variables w ere measured, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), quantity of protein in 24h urine. Then condi tional logistic regression analysis was performed.Results. Some factors, including history of hypertension, longer duration of hy pertension, higher levels of the past highest SBP and DBP, were independently as sociated with the occurrence risk of diabetic nephropathy (DN). Their correspond ing odd ratios (OR) with 95% confidence intervals (CI) were 2.00(1.17～3.43), 1 .25(1.08～1.46), 1.38(1.15～1.66), and 1.33(1.09～1.62) respectively, but family history of hypertension was not significantly associated with the development o f DN. When the above mentioned relations were respectively adjusted by some pos sible confounding factors, they still existed.Conclusions. History of hypertension, longer duration of hypertension, higher l evels of the past highest SBP and DBP are independent risk factors for DN in Chi nese NIDDM patients.展开更多
Objective： Diabetic nephropathy （DN） is one of the most common causes of end-stage renal failure. The pathogenesis of progressive renal injury is multifactorial and the mechanism by which hyperglycemia causes micro...Objective： Diabetic nephropathy （DN） is one of the most common causes of end-stage renal failure. The pathogenesis of progressive renal injury is multifactorial and the mechanism by which hyperglycemia causes microangiopathy is still poorly understood. The WNT pathway is activated in DN and regulating β-catenin protein levels is referred to as the canonical Wntβ-catenin pathway. Because the renin angiotensin system has been reported to be an important contributory factor in the pathophysiology of DN, exogenous administration of angiotensin Ⅱ receptor antagonist may be beneficial in counteracting some biochemical or functional changes of DN. The aim of the study was to determine the β-catenin expression and the possible protective effects of irbesartan, an angiotensin Ⅱ type 1 receptor blocker （ARB） in a rat model of streptozotocin（STZ）-induced diabetic nephropathy. Methods： STZ-induced DN in rats was assessed biochemically by measuring urine volume, protein and creatinine clearance as well as Kidney weight/body weight （KW/BW） and the index of mesangial expansion. Three groups of male Sprague-dawley rats were used. The first group consisted of non-diabetic control rats （control）. The second group was the untreated diabetic rats（STZ＋vehicle）. The third group consisted of diabeti rats treated with irbesartan, 50 mg/kg for 12 weeks （STZ＋irbesartan）. Immunohistochemical stainings and real time PCR for β-catenin were performed in renal cortex of rat modals. Results： Marked hyperglycemia, polyuria, proteinuria, renal hypertrophy, mesangial matrix expansion and glomerular hyperfiltration were observed in STZ diabetic rats. The levels of microalbuminuria and KW/BW in the STZ＋irbesartan group were lower than those in the STZ＋vehicle group （P〈0.05）. The up-regulated immunostaining and mRNA expression of β-catenin were decreased in renal cortic of the Irbesartan-treated diabetic group, but there was no significant difference compared to the untreated diabetic group. Conclusion： The data suggest that irbesartan ameliorates proteinuria and renal hypertrophy, charactered damages of STZ-induced early-stage DN in rats, but its effective drug target is not to inhibit the up-regulated expressions of β-catenin.展开更多
Objective： To observe the podocyte injury in diabetic nephropathy （DN） patients by identifying the urinary podocytes and the situation of detached podocytes in glomeruli and to demonstrate the correlation between p...Objective： To observe the podocyte injury in diabetic nephropathy （DN） patients by identifying the urinary podocytes and the situation of detached podocytes in glomeruli and to demonstrate the correlation between podocyte excretion and proteinuria, blood glucose, serum creatinine in different phases in DN patients. Methods： Urinary podocytes and the podocalyxin （PCX） expression state of podocytes in glomeruli were identified and observed by indirect immunofluorescent method. The DN patients were divided into three groups according to the volume of proteinuria, namely small, medium and large volume proteinuria groups. The podocytes in the urine of every group were calculated. The DN patients were divided into five groups according to the chronic kidney disease （CKD） phases, then the positive podocytes in urine were calculated. Meanwhile, the 24-hour protein in urine, fasting blood glucose （FBG） and the serum creatinine of DN patients were tested. The correlations among the proteinuria, serum creatinine, FBG and the number of positive podocytes in the urine of DN patients were statistically analyzed. Results： Urinary positive podocytes were found in 88% of the patients with DN, whereas podocytes were found in 0% of patients with minimal changed disease （MCD） and healthy cases. The expression of PCX was absent in DN patients. In contrast, PCX was expressed integrally in MCD patients. The positive podocytes was 1.49±0.95/ml in small-volume proteinuria group, 2.15±0.70/ml in the medium-volume proteinuria group, and 3.48±1.27/ml in the large-volume proteinuria group. There was no significant difference between the small- and medium- volume proteinuria groups, and there were significant differences between other groups （P〈0.05）. The positive podocyte number tended to increase as proteinuria was increased. By Pearson analysis, the correlation between podocyte number and proteinuria was podocytes in urine from different groups of DN patients, CKD pc I sitive statistically. The difference of the number of positive -V group was significant statistically. The correlation between serum creatinine of CKD Ⅰ -Ⅲ group and positive podocytes in urine was positive statistically. The correlation between serumcreatinine of CKD Ⅳ- Ⅴ group and positive podocytes in urine was not significant statistically. The correlation between FBG and positive podocytes in urine was not significant either. Conclusion： The mechanism of the podocyte injury in DN patients is present. The podocyte injury in DN may positively correlate to proteinuria and serum creatinine of CKD Ⅰ -ⅢDN patients, but not to the FBG and serum creatinine of CKD Ⅳ-Ⅴ patients.展开更多
AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA scree...AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS:A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital,Sun Yat-sen University from 2022 to 2023 were included,including 95 first-diagnosed DR patients and 105 patients without DR,and all patients underwent OCTA examination and a collection of demographics and renal function parameters.After a quality check,automated measurements of the foveal avascular zone area,vessel density(VD),and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS:Using random forest and multivariate Logistic regression methods,we developed a diagnostic model for DR based on 12 variables(age,FBG,SBP,DBP,HbA1c,ALT,ALP,urea/Scr,DM duration,HUA,DN,and CMT).Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window,AUC=0.837 vs 0.819,P=0.03).In the study of DN patients,the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD;outer VD;full VD;outer PD;full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model.Meanwhile,compared with the 3 mm×3 mm window,the microvascular parameters in the 6 mm×6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.展开更多
Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinica...Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3. I software. Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h (-100.748 to-54.256), -5.002 mmHg [-9.630 to 0.685],-2.949 mmHg (-4.005 to 1.892). -4.284 mmHg (-5.444 to 3.123) respectively. Using clinical albuminuria as the end-point, the pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure. diastolic blood pressure or mean arterial blood pressure. Conclusion: ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.展开更多
Objective To explore the influence of Linggui Zhugan Decoction(LGZGD) on high glucose induced podocyte autophagy.Methods LGZGD containing serum was prepared by intragastric administation of 4.2 g/kg(low dose), 8.4 g/k...Objective To explore the influence of Linggui Zhugan Decoction(LGZGD) on high glucose induced podocyte autophagy.Methods LGZGD containing serum was prepared by intragastric administation of 4.2 g/kg(low dose), 8.4 g/kg(medium dose), and 12.6 g/kg(high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 podocyte cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Both podocytes were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using Western blot.Results Compared with the control group, the proliferation and migration of MPC5 and AB8/13 cells in the high glucose group slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the better effect(P < 0.05). Flow cytometry showed that the medium dose LGZGD group had a significantly lower apoptosis rate(P < 0.05) and higher survival rate(P > 0.05) compared to the high dose LGZGD group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to G2 phase. High dose LGZGD significanly reduced high glucose-increased autophagosome formation in both podocytes(P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3II/I, and P62 expressions were increased in MPC5 cells treated with high glucose and reversed after adminstration of low and medium doses of LGZGD(P < 0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.展开更多
To evaluate the role of glucose transporter- l (GLUT1) in the glucose uptake of glomerular mesangial cells. Methods. Cultured C57/SJL mouse mesangial cells were used in the study. The expression of GLUT1 mRNA was dete...To evaluate the role of glucose transporter- l (GLUT1) in the glucose uptake of glomerular mesangial cells. Methods. Cultured C57/SJL mouse mesangial cells were used in the study. The expression of GLUT1 mRNA was detected by RT- PCR. The expression of GLUT1 protein was detected by immunofluorescence and flow cytometry. The uptake of glucose and its kinetics were determined by 2- deoxy- [3H]- D- glucose uptake. Results. Both GLUT1 mRNA and protein were found in mouse glomerular mesangial cells. 2- deoxy- D- glucose uptake and kinetics assay showed that this glucose transporter had high affinity for glucose and the glucose uptake specificity was further confirmed by phloretin. Conclusion. Functional GLUT1 did present in mouse mesangial cells cultured in vitro and it might be the predominant transporter mediated the uptake of glucose into mesangial cells.展开更多
基金supported by the Open Fund of State Key Laboratory of Tea Plant Biology and Utilization (SKLTOF20200127 and SKLT0F20200108)the Open Fund of Key Laboratory of Tea Plant Resources Comprehensive Development in South Henan Province (HNKLTOF2020005)the Zhejiang Provincial Basic Public Welfare Research Program Project (LGF20H280007)。
文摘Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions(1/100 and 1/50, m/V)as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis(lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism(higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis(lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans.
基金supported by grants from the Joint construction project of Henan Province(SB201901015)the General Program of the National Natural Science Foundation of China General Project(81970633)+2 种基金the Major public welfare special projects in Henan Province(201300310600)the National Natural Science Young Scientists Foundation of China(81800648)the Excellent Young Scientists Fund Program of the Natural Science Foundation of Henan Province(202300410363)。
文摘Background: LncRNA AK044604(regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy(DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury.Methods: Diabetic db/db mice received Risa-inhibition adeno-associated virus(AAV) via tail vein injection, and intraperitoneal injection of lithium chloride(LiCl). Blood, urine, and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells(MPCs) were cultured and treated with Risa-inhibition lentivirus(LV), EX-527, and LiCl. MPCs were collected under different stimulations as noted. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blotting analysis, transmission electron microscopy,Periodic Acid-Schiff staining, and immunofluorescence staining.Results: Risa and activated GSK3β were overexpressed, but Sirt1 was downregulated in DN mice and high glucosetreated MPCs(P<0.001, db/m vs. db/db, NG or HM vs. HG), which was correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1(P<0.001, db/m vs. db/db, NG or HM vs. HG). In contrast, Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury, which could be abrogated by EX-527(P<0.001, db/db+Risa-AAV vs. db/db, HG+Risa-LV vs. HG). Furthermore, LiCl treatment could restore GSK3β-mediated autophagy of podocytes(P<0.001, db/db+LiCl vs. db/db, HG+LiCl vs. HG), suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy.Conclusions: Risa could inhibit autophagy by regulating the Sirt1/GSK3β axis, thereby aggravating podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.
基金supported by the National Nature Science Foundation of China(81771152)National Key R&D Plan(No.2017YFC1702500)the Beijing Joint Project for the Central-Affiliated University(2017-01)。
文摘(+)-Catechin(CE)is mainly found in green and black tea and has many biological effects,such as antiinflammatory,anti-cancer,anti-viral effects,protecting human organs,especially the kidney.This study aims to identify the circRNAs induced by CE in db/db mice and their roles in diabetic nephropathy progression.After the db/db mice were treated with CE,RNA-seq was performed to identify the differentially expressed circRNA and mRNAs.The ceRNA regulatory network was constructed and analyzed using bioinformatics software and public databases(Cytoscape,Clue GO,Mi RWalk,STRING,et al.).Our results revealed that 6 differentially expressed circRNAs are most associated with the cholinergic synapse,neurotrophin signaling pathway,and insulin signaling pathway.Among these,circRNA.5549 and circRNA.4712 might regulate Cd36,Cyp26 b1,C8 a,Cyp2 j13,Grem2 genes through ceRNA regulatory mechanism in the presence of CE treatment.The expanded network of proteins interacting with these 5 genes shows that the TGF-βsignaling pathway,signaling pathways regulating pluripotency of stem cell,fat digestion and absorption,and PPAR signaling pathway was highly enriched.Overall,circRNA.5549 and circRNA.4712 exhibit a promotive function in CE-treated db/db mice,especially in circRNA.5549/miR-29a-5P/Cd36 regulatory network,and this evidence suggest that their ceRNA regulatory network might be a therapeutic target for DN in humans.
文摘To assess the role of hypertension and family history of hypertensio n in the development of nephropathy in patients with non insulin dependent dia betes mellitus (NIDDM).Methods. A retrospective analysis was done on 2 groups of NIDDM patients, one g roup without proteinuria (urine protein< 300mg/24h, n=106) and the other group w ith proteinuria (urine protein≥500mg/24h, n=106). The 2 groups were matched by age(≤±3yrs), sex, ethnic and resident place. Some information of these subject s including demographic; history of disease, family history of diseases, lifesty le and behavior style variables was obtained by questionnaire; some variables w ere measured, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), quantity of protein in 24h urine. Then condi tional logistic regression analysis was performed.Results. Some factors, including history of hypertension, longer duration of hy pertension, higher levels of the past highest SBP and DBP, were independently as sociated with the occurrence risk of diabetic nephropathy (DN). Their correspond ing odd ratios (OR) with 95% confidence intervals (CI) were 2.00(1.17～3.43), 1 .25(1.08～1.46), 1.38(1.15～1.66), and 1.33(1.09～1.62) respectively, but family history of hypertension was not significantly associated with the development o f DN. When the above mentioned relations were respectively adjusted by some pos sible confounding factors, they still existed.Conclusions. History of hypertension, longer duration of hypertension, higher l evels of the past highest SBP and DBP are independent risk factors for DN in Chi nese NIDDM patients.
文摘Objective： Diabetic nephropathy （DN） is one of the most common causes of end-stage renal failure. The pathogenesis of progressive renal injury is multifactorial and the mechanism by which hyperglycemia causes microangiopathy is still poorly understood. The WNT pathway is activated in DN and regulating β-catenin protein levels is referred to as the canonical Wntβ-catenin pathway. Because the renin angiotensin system has been reported to be an important contributory factor in the pathophysiology of DN, exogenous administration of angiotensin Ⅱ receptor antagonist may be beneficial in counteracting some biochemical or functional changes of DN. The aim of the study was to determine the β-catenin expression and the possible protective effects of irbesartan, an angiotensin Ⅱ type 1 receptor blocker （ARB） in a rat model of streptozotocin（STZ）-induced diabetic nephropathy. Methods： STZ-induced DN in rats was assessed biochemically by measuring urine volume, protein and creatinine clearance as well as Kidney weight/body weight （KW/BW） and the index of mesangial expansion. Three groups of male Sprague-dawley rats were used. The first group consisted of non-diabetic control rats （control）. The second group was the untreated diabetic rats（STZ＋vehicle）. The third group consisted of diabeti rats treated with irbesartan, 50 mg/kg for 12 weeks （STZ＋irbesartan）. Immunohistochemical stainings and real time PCR for β-catenin were performed in renal cortex of rat modals. Results： Marked hyperglycemia, polyuria, proteinuria, renal hypertrophy, mesangial matrix expansion and glomerular hyperfiltration were observed in STZ diabetic rats. The levels of microalbuminuria and KW/BW in the STZ＋irbesartan group were lower than those in the STZ＋vehicle group （P〈0.05）. The up-regulated immunostaining and mRNA expression of β-catenin were decreased in renal cortic of the Irbesartan-treated diabetic group, but there was no significant difference compared to the untreated diabetic group. Conclusion： The data suggest that irbesartan ameliorates proteinuria and renal hypertrophy, charactered damages of STZ-induced early-stage DN in rats, but its effective drug target is not to inhibit the up-regulated expressions of β-catenin.
文摘Objective： To observe the podocyte injury in diabetic nephropathy （DN） patients by identifying the urinary podocytes and the situation of detached podocytes in glomeruli and to demonstrate the correlation between podocyte excretion and proteinuria, blood glucose, serum creatinine in different phases in DN patients. Methods： Urinary podocytes and the podocalyxin （PCX） expression state of podocytes in glomeruli were identified and observed by indirect immunofluorescent method. The DN patients were divided into three groups according to the volume of proteinuria, namely small, medium and large volume proteinuria groups. The podocytes in the urine of every group were calculated. The DN patients were divided into five groups according to the chronic kidney disease （CKD） phases, then the positive podocytes in urine were calculated. Meanwhile, the 24-hour protein in urine, fasting blood glucose （FBG） and the serum creatinine of DN patients were tested. The correlations among the proteinuria, serum creatinine, FBG and the number of positive podocytes in the urine of DN patients were statistically analyzed. Results： Urinary positive podocytes were found in 88% of the patients with DN, whereas podocytes were found in 0% of patients with minimal changed disease （MCD） and healthy cases. The expression of PCX was absent in DN patients. In contrast, PCX was expressed integrally in MCD patients. The positive podocytes was 1.49±0.95/ml in small-volume proteinuria group, 2.15±0.70/ml in the medium-volume proteinuria group, and 3.48±1.27/ml in the large-volume proteinuria group. There was no significant difference between the small- and medium- volume proteinuria groups, and there were significant differences between other groups （P〈0.05）. The positive podocyte number tended to increase as proteinuria was increased. By Pearson analysis, the correlation between podocyte number and proteinuria was podocytes in urine from different groups of DN patients, CKD pc I sitive statistically. The difference of the number of positive -V group was significant statistically. The correlation between serum creatinine of CKD Ⅰ -Ⅲ group and positive podocytes in urine was positive statistically. The correlation between serumcreatinine of CKD Ⅳ- Ⅴ group and positive podocytes in urine was not significant statistically. The correlation between FBG and positive podocytes in urine was not significant either. Conclusion： The mechanism of the podocyte injury in DN patients is present. The podocyte injury in DN may positively correlate to proteinuria and serum creatinine of CKD Ⅰ -ⅢDN patients, but not to the FBG and serum creatinine of CKD Ⅳ-Ⅴ patients.
文摘AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS:A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital,Sun Yat-sen University from 2022 to 2023 were included,including 95 first-diagnosed DR patients and 105 patients without DR,and all patients underwent OCTA examination and a collection of demographics and renal function parameters.After a quality check,automated measurements of the foveal avascular zone area,vessel density(VD),and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS:Using random forest and multivariate Logistic regression methods,we developed a diagnostic model for DR based on 12 variables(age,FBG,SBP,DBP,HbA1c,ALT,ALP,urea/Scr,DM duration,HUA,DN,and CMT).Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window,AUC=0.837 vs 0.819,P=0.03).In the study of DN patients,the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD;outer VD;full VD;outer PD;full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model.Meanwhile,compared with the 3 mm×3 mm window,the microvascular parameters in the 6 mm×6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.
文摘Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3. I software. Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h (-100.748 to-54.256), -5.002 mmHg [-9.630 to 0.685],-2.949 mmHg (-4.005 to 1.892). -4.284 mmHg (-5.444 to 3.123) respectively. Using clinical albuminuria as the end-point, the pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure. diastolic blood pressure or mean arterial blood pressure. Conclusion: ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.
基金supported by Guangdong Bureau of Traditional Chinese Medicine (20211082)
文摘Objective To explore the influence of Linggui Zhugan Decoction(LGZGD) on high glucose induced podocyte autophagy.Methods LGZGD containing serum was prepared by intragastric administation of 4.2 g/kg(low dose), 8.4 g/kg(medium dose), and 12.6 g/kg(high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 podocyte cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Both podocytes were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using Western blot.Results Compared with the control group, the proliferation and migration of MPC5 and AB8/13 cells in the high glucose group slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the better effect(P < 0.05). Flow cytometry showed that the medium dose LGZGD group had a significantly lower apoptosis rate(P < 0.05) and higher survival rate(P > 0.05) compared to the high dose LGZGD group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to G2 phase. High dose LGZGD significanly reduced high glucose-increased autophagosome formation in both podocytes(P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3II/I, and P62 expressions were increased in MPC5 cells treated with high glucose and reversed after adminstration of low and medium doses of LGZGD(P < 0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.
基金This work was supported by the National Natural Science Foundation of China (No.39870288)
文摘To evaluate the role of glucose transporter- l (GLUT1) in the glucose uptake of glomerular mesangial cells. Methods. Cultured C57/SJL mouse mesangial cells were used in the study. The expression of GLUT1 mRNA was detected by RT- PCR. The expression of GLUT1 protein was detected by immunofluorescence and flow cytometry. The uptake of glucose and its kinetics were determined by 2- deoxy- [3H]- D- glucose uptake. Results. Both GLUT1 mRNA and protein were found in mouse glomerular mesangial cells. 2- deoxy- D- glucose uptake and kinetics assay showed that this glucose transporter had high affinity for glucose and the glucose uptake specificity was further confirmed by phloretin. Conclusion. Functional GLUT1 did present in mouse mesangial cells cultured in vitro and it might be the predominant transporter mediated the uptake of glucose into mesangial cells.
