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The Renal Expression Of Adiponectin Receptor 1 In Type 2 Diabetic Rats And The Intervention Study Of Telmisartan

Posted on:2010-02-17Degree:MasterType:Thesis
Country:ChinaCandidate:P WeiFull Text:PDF
GTID:2144360275961439Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective In this study, type 2 diabetic rat model was induced by feeding Wistar rats with high-sugar-high-fat diet and then injection of a low dose of streptozotocin (STZ) by abdominal cavity.We investigated the expression of adiponectin receptor 1(AdipoR1) in renal tissue of type 2 diabetic rats and the effect of telmisartan on its expression in order to explore the protective mechanism of telmisartan.Methods Ten of thirty-six Wistar rats were randomly taken out to be normal control group (group A, n=10) and the rest were made for type 2 diabetic.The normal control rats were fed with standard diet while the diabetic rats were fed with high-sugar-high-fat diet (mixed 2.5%cholesterin, 20%sugar, 18%cooked lard and standard diet together). Four weeks later, 30 mg/kg STZ was injected into diabetic abdominal cavity to destroy pancreas while the normal control group was injected with equivalent volume of citric acid buffer by abdominal cavity. At the end of 6 weeks, the rats with fasting blood glucose (FBG)≥7.8mmol/l and insulin resistance were considered as type 2 diabetic models. All diabetic rats were randomly divided into 2 groups: T2DM model rats (group B, n=10) and T2DM model rats treated with telmisartan (group C, n=10).The rats in group C were given telmisartan for twelve consecutive weeks. At the end of this experiment, body weight, FBG, FINS, TG, TC, BUN and Cr were measured. 24 hour urinary albumin excretion rate were assayed. The pathological changes of kidney were examined by light microscop. Renal protein expressions of MCP-1, NF-κB, GLUT-1, TGF-β1 and AdipoR1 were measured by immunohistochemistry. The expression of AdipoR1 mRNA was measured by RT-PCR.Results FBG, FINS, TG, TC, BUN, Cr, 24 hour urinary albumin excretion rate and kidney weight/body weight in T2DM rats (group B) were all significantly higher in group B than those in group A(P<0.05). Telmisartan could reverse all those changes in diabetic rats. The renal expression of AdipoR1 mRNA was significantly lower in group B than that in group A (P<0.01). After telmisartan treatment, the expression of AdipoR1 mRNA was notably higher in group C than that in group B (P<0.01).Immunohistoehemisty showed that the expressions of MCP-1, NF-κB, GLUT-1, TGF-β1 in renal tissue in diabetes groups were much higher than those in the normal control group (P<0.01). Compared with group B, the expressions of MCP-1, NF-κB, GLUT-1, TGF-β1 in renal tissue in group C were markedly lower (P<0.01). Conclusion (1) The expression of AdipoR1 in T2DM rats is markedly lower in renal tissue. It indicates that AdipoR1 is closely related to the occurrence and development of DN.(2) Telmisartan can correct the disturbance of glucose and lipid metabolism, increase insulin sensitivity in T2DM rats. Telmisartan can increase the expression of AdipoR1 in renal tissue of T2DM rats, and reduce the expression of MCP-1, NF-κB, GLUT-1, TGF-β1 in renal tissue of T2DM rats. These results suggested that telmisartan could have a protective effect on kidney by increasing the renal expression of AdipoR1 in type 2 diabetic rats.
Keywords/Search Tags:adiponectin receptor 1, type 2 diabetic, telmisartan, diabetic nephropathy
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