海参虫草复剂对糖尿病大鼠肾脏保护作用机制的研究

目的研究海参虫草复剂(AC)对链脲佐菌素(Streptozocin,STZ)诱导的糖尿病大鼠肾脏保护作用机制。方法采用一次性腹腔注射STZ的方法建立糖尿病大鼠模型,经过长期高血糖环境下饲养造成肾脏损伤。灌胃AC8周后,分别检测大鼠空腹血糖、肾脏指数、24h尿微量白蛋白排泄率(UAER)及肾脏的氧化应激水平;采用RT-PCR法测定肾脏中转化生长因子β1(TGF-β1)及其Ⅱ型受体(TβRⅡ)、结缔组织生长因子(CTGF)mRNA表达。Western blot方法检测肾脏中TGF-β1蛋白表达,免疫组化法检测肾脏中Ⅳ型胶原蛋白表达。结果 AC能降低糖尿病大鼠空腹血糖、肾脏指数和UAER(P<0.05,P<0.01),提高肾脏抗氧化能力,下调TGF-β1、TGFβRⅡ和CTGF的mRNA表达(P<0.05,P<0.01),降低TGF-β1及Ⅳ型胶原的蛋白表达水平(P<0.01)。结论 AC可通过改善糖尿病大鼠肾脏氧化应激状态,抑制TGF-β1、TβRⅡ和CTGF基因表达,以减少尿蛋白排泄及阻止肾脏肥大,从而达到保护肾脏的作用。

The mechanism of the mixture of Apostichopus japonicus and Cordyceps militaris on protection of renal injury in diabetic rats

Aim To study the mechanism of the mixture of Apostichopus japonicus and Cordyceps militaris(AC) on protection of renal injury in diabetic rats.Methods Rat diabetic model,in which the kidneys were damaged under long-term high levels of blood glucose,was induced by a single intraperitoneal injection of Streptozotocin.The diabetic rats were given differen dosages of AC daily for 8 weeks,and indices including fasting blood glucose,the kidney index,UAER,the level of MDA,SOD,CAT and GSH-PX were determined.The TGF-β1,TGFβRⅡ and CTGF mRNA expression in the kidney were assessed by semi-quantity RT-PCR.The expression of collagen Ⅳ and TGF-β1 protein in the kidney were detected by immunohistochemistry or Western blot analysis.Results The AC had remarkably suppressed hyperglycemic,kidney atrophy index,UAER and the level of MDA(P < 0.05,P < 0.01),and improved the level of SOD and CAT in kidney(P < 0.05,P < 0.01).The expressions of TGF-β1,TGFβRⅡ and CTGF mRNA were markedly up regulated in kidney of diabetic rats,which were effectively suppressed by AC treatment(P < 0.01).Western blot and immunohistochemistry analysis showed that the expression of TGF-β1 and collagen Ⅳ protein was reduced significantly by AC treatment.Conclusion It suggests that the beneficial effect of AC on renal injury may result from its antioxidative property and inhibiting TGF-β1,TGFβRⅡ and CTGF expression.