Effects of rosiglitazone on the expression of matrix metalloproteinases-2,9 and collagen IV in renal cortex of diabetic rats
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Objective: To investigate the effects of rosiglitazone on the expression of matrix metalloproteinases-2,9(MMP-2,MMP-9)and collagen IV(C-IV) in renal cortex of diabetic rats. Methods: Forty Sprague -Dawley rats were randomly divided into 3 groups:normal control group (C group),diabetes mellitus group(DM group)and rosiglitazone-treated diabetes mellitus group(DR group). Diabetic model was induced by streptozocin(STZ), and the rats in DR group received rosiglitazone through stomach perfusion.The expression of MMP-2,MMP-9 and C-IV in the renal cortex was studied by immunohistochemistry. Changes of glomerulus were observed by using light microscope and electron microscope in three groups. Results: Compared with those in C group,the expression of MMP-2,MMP-9 in renal cortex was lower ,while that of C-IV was higher(P 0.01). The pathologic changes of glomerulas were significantly serious in DM group . The pathologic changes in DR group were improved by streptozocin treatment(P 0.01). Conclusion: MMP-2 and MMP-9 play an important role in the fomation of diabetic extracellular matrix. Rosiglitazone has protective effects on the kidneys of diabetic rats partly through upregulating MMP-2 and MMP-9 and decreasing C-IV accumulation in renal cortex.Keywords:
Rosiglitazone
Streptozocin
Renal cortex
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ObjectiveTo observe the effects of rosiglitazone on kidney damage in streptozotocin induced diabetic rats.MethodsForty male Sprague-Dawley rats were randomized into 3 groups: normal control rats(group C,n=10),diabetic rats(group DC,n=15) and treated diabetic rats(group DR,n=15).The dibetes was induced with streptozotocin(STZ) 60 mg·kg-1 ip;the diabetic rats were treated with axenic rosiglitazone 4 mg·kg-1 in water by mouth qd.Blood glucose,HbA1c,BUN,microalbuminuria and kidney pathological changes were examined 10 weeks after treatment.ResultsThe pathological changes of kidney in group DC included stenosis or occlusion of capillaries,proliferation of mesangial cells and thickening of glomerular basement membrane;all of these changes got improved after treatment in group DR.The levels of urea nitrogen and microalbuminuria were significantly lower in group DR than in group DC,but still higher than in group C(P0.01).ConclusionRosiglitazone can improve or retard the nephropathology in diabetic rats,exerting certain protective effects on the kidney.
Rosiglitazone
Microalbuminuria
Blood urea nitrogen
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Objective To investigate the expression of matrix metalloproteinase-9(MMP-9)in kidney of diabetic rats.Methods 20 adult SD rats were randomly divided into normal control group(NC)and diabetic model group(DM).After diabetic model rats were induced by streptozotocin(STZ),the morphological changes were observed through the light microscope and immunohistochemical staining was employed to detect the expression of MMP-9 in kidney and analyzed with image analysis system.Results The morphological changes of the glomeluri of diabetic rats were obvious,but with the normal structure of the normal rats.The expression of MMP-9 in diabetic kidneys was significantly lower than that in normal control rats(P0.05).Conclusion Downexpression of MMP-9 in renal glomeluri in diabetic rats may promote the accumulation of extracellular matrix in kidney.
Normal group
Matrix (chemical analysis)
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【Objective】To explore the effect of rosiglitazone on expressions of E-cadherin and β-catenin in renal tubular epithelial cells of diabetic nephropathy rats,and to elucidate the possible renal-protective mechanisms of rosiglitazone.【Methods】Twenty-four male Wistar rats were randomly divided into 3 groups: normal control group(n=8),diabetic model group(n=8),and rosiglitazone treatment group [rosiglitazone 4 mg/(kg·d),n=8].During the experiment,all the rats were feed with standard diet.After 12 weeks,their heights,blood glucose and cholesterol levels were compared,while the pathology change and expressions of E-cadherin and β-catenin in renal tubular epithelial cells were detected respectively by HE and RT-PCR.【Results】Rosiglitazone significantly decreased blood glucose level(P0.01).The tubal injury index significantly increased in the diabetic model group(P0.01),while after treatment by rosiglitazone,renal pathology change improved(P0.05).Expressions of E-cadherin and β-catenin in renal tubular epithelial cells were lower in the diabetic model group,while their expressions in rosiglitazone treatment group were significant higher than those in diabetic model rats(P0.01).【Conclusion】Rosiglitazone can protect the renal tubular epithelial by up-regulatingβ-catenin expression.
Rosiglitazone
Renal pathology
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AIM:To observe the effects of exendin-4 on the expression of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1) in the renal tissue of type 2 diabetic rats. METHODS:The rat model of type 2 diabetes mellitus was set up by a combination of high fat diat and low dose streptozotocin(STZ). The diabetic rats were randomly divided into 4 groups :diabetes mellitus group(DM group),low dose of exendin-4 group(EL group),middle dose of exendin-4 group(EM group),high dose of exendin-4 group(EH group). Normal control group(NC group) was also established. After 6 weeks,the expression of MMP-9 and TIMP-1 in renal tissue was measured by immunohistochemistry. RESULTS:The expression of MMP-9 and TIMP-1 in DM group was higher than that in NC group(P0.01),while the expression of MMP-9 and TIMP-1 in all doses of exendin-4 groups was lower than that in DM group(P0.01). CONCLUSION:Exendin-4 has some renoprotective effect on type 2 diabetic rats,partly through down-regulating the expression of MMP-9 and TIMP-1.
Matrix metalloproteinase 9
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【Objective】 To observe the effects of Valsartan on expression of MMP-9/TIMP-1 in renal tubular epithelial cells of diabetic nephropathy rats,elucidate the possible renal-protective mechanisms of Valsartan.【Methods】 Thirty male Wistar rats were randomly divided into 3 groups: normal control group(n =10),diabetic model group(n =10),and Valsartan treatment group(Valsartan 30 mg/kg·d,n =10).Five rats of each group were killed respectively at 8,16 weeks.The pathologic change and expressions of ILK and MMP-9/TIMP-1 in renal tubular epithelial cells were detected.【Results】 Comparing with the control group,renal tubular-interstitial lesions in the diabetic model group is significantly aggravated,the TGF-β1,MMP-9,TIMP-1 expressions elevated while the MMP-9/TIMP-1 ratio declined.The changes mentioned above in the Valsartan treatment group is significantly smaller than in diabetic model rats.【Conclusions】 MMP-9/TIMP-1 imbalance is one possible factor in the progress of renal interstitial fibrosis in diabetes mellitus.Valsartan can improve the process of renal tubular-interstitial lesions by regulating MMP-9/TIMP-1 level.
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The changes in matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were examined in the kidneys of diabetic rats to investigate the degradative pathway of collagen type IV (C-IV) and the protective effects of pioglitazone on an experimental model of diabetic nephropathy.In 54 SD rats used in our study, 18 served as normal controls. Diabetes mellitus was induced in 36 age- and weight-matched rats by intraperitoneal injection of streptozotocin (70 mg/kg); 18 of the diabetic rats were allocated at random to receive pioglitazone [20 mg.kg(-1).d(-1)] in their drinking water and 18 served as diabetic controls. Rats were killed after 2, 4, or 8 weeks of treatment. Kidneys were examined pathomorphologically and the expressions of MMP-2, MMP-9, and C-IV were analyzed by immunohistochemistry, and the results were quantified by image analysis techniques.Diabetes mellitus was associated with a decrease in the expression of MMP-2 in the glomeruli (P < 0.05, vs control). By contrast, MMP-2 expression in the interstitium increased, but not significantly (P > 0.05, vs control). The expression of MMP-9 did not show any change when comparing the three groups (P > 0.05, vs control). STZ-diabetic rats were also associated with an increase in the expression of C-IV in the glomeruli and the interstitium (P < 0.05, vs control). All diabetes-associated changes in MMP-2 expression were attenuated by pioglitazone treatment in association with reduced C-IV accumulation.These results indicate that a decrease in MMP-2 expression in the glomeruli of diabetic rats may lead to impairment of C-IV degradation and contribute to the matrix accumulation in diabetic nephropathy. Pioglitazone treatment, which can attenuate the decrease of glomerular MMP-2 and the increase of C-IV degradation, has curative effects on diabetic nephropathy.
Pioglitazone
Intraperitoneal injection
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Objective To investigate the effects of rosiglitazone on renal TGF-β and collagen-Ⅳ in diabetic rats.Methods Forty rats were randomized into 3 groups of normal control rats(group C),diabetic rats(group DC)and diabetic rats treated with rosiglitazone(group DR).After 10 weeks,blood glucose and microalbuminuria were measured and pathologic change of the kidney was observed.TGF-β and collagen-Ⅳ expressions in kidneny cortex were observed by immunohistochemistry.Results Kidney index,microalbuminuria and the expressions of TGF-β and collagen-Ⅳ in group DC were significantly higher than those in group C and group DR(P0.01).Conclusion Rosiglitazone has a protective effect on the kidney in diabetic rats through downregulating the expression of TGF-β and collagen-Ⅳ.
Rosiglitazone
Microalbuminuria
Renal cortex
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Objective To investigate the effects of benazepril on expressions of matrix metallopro teinase-2, tissue inhibitor of metalloproteinase-2 and collagen IV (C-IV) in the kidney of diabetic rats. Methods Forty Sprague -Damly rats were randomly divided into three groups: the control group (C group), diabetes mellitus group (DM group) and diabetic group treated with benazepril (10mg/kg)(DB group). Eight weeks later, expression of MMP-2, TIMP-2 and C-IV in the kidney tissure was determined by immunohistochemistry method (SP)and RT-PCR. Results Compared with C group, expressions of protein and mRNA MMP-2 significantly reduced in the glomeruli,while expressions TIMP-2 and C-IV were increased in the DM group (P0.01). Meanwhile, the pathologic changes of the glomeruli were serious in DM group. The abnormal expressions of these proteins, mRNA and pathologic changes were dramatically improved in diabetic rats by benazepril treatment (P0.01). Conclusion Benazepril can exert protective effects on diabetic nephropathy, partly through upregulating MMP-2 and decreasing TIMP-2, C-IV accumulation in renal cortex.
Benazepril
Matrix metalloproteinase 9
Renal cortex
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AIM:To observe the effect of rosiglitazone on serum resistin level and to investigate the possible mechanism of glomerular sclerosis in type 2 diabetic rats.METHODS:Ten-week-old Wistar rats were divided into diabetic nephropathy(DN) group(10 cases) and DN+rosiglitazone group(10 cases).The other 10 Wistar rats were used as normal control group.Type 2 diabetic rats were induced by cutting the right kidney and injecting small dose(35 mg/kg) of streptozocin(STZ).Rosiglitazone group received rosiglitazone 10 mg·kg-1·d-1 while normal control group and DN group were fed with normal chow diet.After 20 weeks,vessel blood was collected for plasma IL-1,TNF-α and resistin assayed by ELISA.The serum levels of glucose,creatinine,urea nitrogen and microalbum of 24 h urine were also detected.The expression of TGF-β1 in glomerulus was examined by immunohistochemistry.Smad2 phosphatase activity was detected by Western blotting.RESULTS:The plasma IL-1,TNF-α,hs-CRP and resistin,and microalbum of 24 h urine in rosiglitazone group,were significantly lower than those in DN group while the serum level of glucose was not different from that in DN group.The expression of TGF-β1 and phosphorylated level of Smad2 were lower in rosiglitazone group than those in DN group.The degree of glomerular sclerosis in rosiglitazone group was obviously lighter than that in DN group.CONCLUSION:Rosiglitazone delays and ameliorates the development of diabetic glomerular sclerosis.The mechanism is possibly related to the modulation of resistin and other inflammatory factors.Anti-inflammation is a potential way for controlling diabetic nephropathy.
Rosiglitazone
Resistin
Blood urea nitrogen
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Objective To observe the changes of the expression of metalloproteinase(MMP)-9 at kidney with the development of diabetic nephropathy(DN) in streptozotocin(STZ)-induced diabetic rats and to investigate their correlation.Methods Sixteen female Wistar rats were used to induce diabetes mellitus by intraperitoneal injection of STZ(60 mg/kg).Immunohistochemistry was used to detect MMP-9 expressions in kidneys with image analysis system on the 4th and 8th weeks.Results In this experiment,the expression of MMP-9 in diabetic kidneys on the 4th and 8th weeks(8.2±0.9,3.9±0.6) were both significantly lower than that in normal control rats(15.6±73.4,16.2±3.1,P0.01),and the level on the at 8th week (3.9±0.6) was lower than that on the 4th week(8.2±0.9,P0.01).Conclusion The reduced expression of MMP-9 is one of the main reasons for impairing renal structure of DN.
Matrix metalloproteinase 9
Intraperitoneal injection
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