Protective effect of exenatide on podocyte in diabetic nephropathy mice / 中华内分泌代谢杂志

ABSTRACT

Objective:To investigate the effects of exenatide on podocyte in diabetic nephropathy mice.Methods:Diabetic nephropathy mice models were induced by using streptozocin-treated C57BL/6J mice on high fat diets, which were randomized by random number table to diabetic nephropathy control group (DN group, n=8) and exenatide treatment diabetic nephropathy group (DN+ Ex group, n=8). The C57BL/6J mice on normal chow diet were used as normal control group (NC group, n=8). After the intervention, blood glucose, renal function, and urine albumin/creatinine ratio were measured. Pathological glomerular changes were observed by pexiodic acid-Schiff stain (PAS) staining. The mRNA expression of profibrotic molecules Collagen Ⅳ, transforming growth factor-β (TGF-β), and Fibronectin in glomerular lysates were measured by realtime quantitative PCR (RT-PCR). Podocyte injury and apoptosis were evaluated by immunofluorescent staining and transmission electron microscopy. The expression of Nephrin, Cleaved caspase-3, protein kinase B (Akt), and phosphorylated Akt (p-Akt) in glomerular lysates were examined by western blotting. Results:Compared with the DN group, urine albumin/creatinine ratio was significantly decreased in the DN+ Ex group ( P<0.01). PAS staining and analysis found that exenatide administration ameliorated mesangial matrix expansion and glomerular hypertrophyin in DN group ( P<0.05). RT-PCR analyses showed that the glomerular expression for Fibronectin, TGF-β, and Collagen Ⅳ were significantly decreased in the DN+ Ex group compared with the DN group ( P<0.01). Immunofluorescent staining and transmission electron microscopy revealed that exenatide treatment improved podocyte injury and apoptosis in DN group. Western blotting analyses showed that exenatide increased the Nephrin expression, decreased the Cleaved caspase-3 expression, increased the p-Akt expression in glomerular lysatesin diabetic nephropathy mice ( P<0.01). Conclusion:Exenatide attenuates podocyte injury and apoptosis and proteinuria, and prevents the progression of diabetic nephropathy mice. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway in glomerular lysates may be related to the protective effects of exenatide.