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

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-2 mRNA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-2 mRNA及蛋白表达降低而TIMP-2 mRNA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-2 mRNA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，从而减轻肾小球细胞外基质沉积也可能是其作用途径之一。

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

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 x 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 TGFbeta1, 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 TGFbeta1 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.