Effect Of Exendin-4on Expression Of TGFβ-1, MT1-MMP In Renal Tissue Of Diabetic Nephropathy Rats

Objective::To observe the effect of exendin-4on the expression of transforming growth factor Beta-1and membrane-type matrixmetalloprotein ase-1in the renal tissues of diabetic nephropathy rats.METHODS:1. model of diabetic nephropathy rats had been established by high-fat and high-suger diet and intraperitoneal injection of a low dose of strptozotocin.the rats were randomly divided into3groups:diabetic nephropathy group, lower dose of exendin-4treatment group and high dose of exendin-4treatment group.2.after of six weeks,24hours proteinuria, blood glucose, and blood lipid were measured;3.kidney tissues pathological changes were observe by microscopy.4.Immunohistochemistry and RT-PCR were used to determine the protein and mRNA expression of TGF-β1,MT1-MMP in renal tissue.5.Statistical analysis:All statistical analysis was performed with Windows SPSS17.0, date are presented X⊥S. Homogeneity of variance between groups compared with the LSD-t test;. Differences were considered significant at a value of P<0.05.RESULTS:1.compared with the diabetic nephropathy group,blood glucose, triglycerides,high density lipoprotein,24h urinary albumin decreased in Exendin-4treatment groups (P<0.05);High-dose of exendin-4treatment group improve more obvious (P<0.01).2. kidney pathological changes of the organization by light-microscopy:glomerular structure disorder, capillary loops under pressure, renal small tube lumen narrowed, wall thickening in the diabetes nephrosis rat model control group;kidney pathological changes reduce by Exendin-4treatment;High-dose of exendin-4treatment group improve more obvious.3.the expression of TGF-β1decreased and the expression of MT1-MMP increased by Exendin-4treatment (P<0.05);High-dose of exendin-4treatment group improve more obvious (P<0.01).CONCLUSION:1. blood glucose, triglycerides,high density lipoprotein,24h urinary albumin decreased by Exendin-4treatment2.the mechanism was related to inhibit the accumulation of extracellular matrix by strengthen MT1-MMP mRNAexpression and reduce TGF-β1mRNAexpression in the renal tissues.3.Exendin-4have some renal protective effect on the diabetic nephropathy rats.