葛根素对糖尿病大鼠肾功能及肾组织MMP-2与TIMP-2表达的影响

Effects of puerarin on renal function, expressions of MMP-2 and TIMP-2 in diabetic rats

目的 探讨葛根素对糖尿病大鼠肾功能及肾组织基质金属蛋白酶 2 (MMP 2 )及其组织抑制剂 2 (TIMP 2 )表达的影响。方法 单侧肾切除大鼠ip链脲佐菌素诱发糖尿病模型。用原位杂交法检测肾小球MMP 2及TIMP 2mRNA表达 ,流式细胞术和免疫组织化学检测肾皮质TGFβ1,MMP 2 ,TIMP 2 ,IV型胶原及层粘连蛋白表达。 结果糖尿病组较对照组肾小球MMP 2mRNA及蛋白表达降低而TIMP 2mRNA及蛋白表达升高 ,TGFβ1,IV型胶原及层粘连蛋白表达亦增加 ,肾功能恶化 ;葛根素用药组较糖尿病组肾小球MMP 2mRNA及蛋白表达升高 ,而TGFβ1,TIMP 2 ,IV型胶原及层粘连蛋白表达减少 ,肾功能改善。结论 葛根素对糖尿病大鼠肾功能具有保护作用 ,除降低血糖外 ,调节肾小球MMP 2及TIMP 2表达 。

Aim To investigate the effect of puerarin on expressions of MMP-2 and TIMP-2 in the kidney of diabetic rats. Methods Uninephrectomized male Wistar rats were used to induce diabetes by intraperitoneal injection of streptozocin (65 mg·kg -1). Puerarin was given daily by intraperitoneal injection from the third day of induction of diabetes for 16 weeks. Using in situ hybridization and immunohistochemistry to detect MMP-2, TIMP-2 mRNA expressions and MMP-2, TIMP-2, collagen IV and Laminin expressions in diabetic kidneys with image analysis system, Flow cytometry was used to detect the expressions of TGFβ1, MMP-2 and TIMP-2. Results Compared with those in kidneys of control group, expressions of MMP-2 mRNA and proteins were lower, while the expressions of both TGFβ1 and TIMP-2 were higher in the diabetic kidney (P<0.05). The level of MMP-2 expression was advanced, while expression of TIMP-2 was reduced by puerarin treatment (P<0.05). Conclusion Puerarin showed some renal protective effect on diabetic nephropathy, partly through inhibition of excessive deposition of glomeruli extracellular matrix by up-regulating MMP-2 and down-regulating TIMP-2 expressions besides reducing the blood glucose.