葛根素对糖尿病大鼠肾功能及肾组织MMP-3、TIMP-1表达的影响

EFFECTS OF PUERARIN ON RENAL FUNCTION AND EXPRESSIONS OF MMP-3 AND TIMP-1 IN THE KIDNEY OF DIABETIC RATS

目的 探讨葛根素对糖尿病大鼠肾小球结构、功能及肾组织基质金属蛋白酶 3(MMP 3)、组织抑制剂 1(TIMP 1)表达的影响。方法 腹腔注射链脲佐菌素诱发大鼠糖尿病模型 ,每日ip葛根素注射液 ,共 16周。采用原位杂交法检测肾小球TIMP 1mRNA表达 ,流式细胞术和免疫组化检测肾皮质MMP 3、TIMP 1及Ⅳ型胶原、层粘连蛋白表达。结果 糖尿病组较对照组肾小球TIMP 1mRNA及蛋白表达增加 ,MMP 3、TIMP 1及Ⅳ型胶原、层粘连蛋白表达亦增加 ;葛根素用药组较糖尿病组TIMP 1mRNA、蛋白及MMP 3、Ⅳ型胶原、层粘连蛋白表达减少。结论 葛根素对糖尿病大鼠肾功能、形态的影响具有保护作用 ,除降低血糖外 ,调节肾小球MMP 3、TIMP 1表达式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。

Objective:To investigate the effects of puerarin on renal structure?function and expressions of MMP-3 and TIMP-1 in the kidney of diabetic rats.Methods:Uninephrectomized STZ-induced male wister rats were used.Puerarin was delivered daily by the intraperitoneal injection from the third day of induction to diabetes for 16 weeks.Using in situ hybridization and immunohistochemistry to detect TIMP-1mRNA expression and MMP-3?TIMP-1?collagen Ⅳ and Laminin expressions in diabetic kidneys with image analysis system;Flow cytometry was used to detect the expressions of MMP-3?TIMP-1.Results:BUN?Ccr and Upro in diabetic rats were significant higher than that in control group.Compared with those in kidneys of control group,diabetic kidneys showed increased expressions of both MMP-3?TIMP-1 proteins and excessive deposition of glomeruli extracellular matrix(P<0.05).The blood glucose and the level of expressions of MMP-3?TIMP-1?collagen Ⅳ and Laminin were reduced by puerarin treatment,renal function was improved.Conclusions:Puerarin has some renal protective effect on diabetic nephropathy partly through inhibition of excessive deposition of glomeruli extracellular matrix by down-regulating MMP-3 and TIMP-1 expressions besides reducing the blood glucose.