二苯乙烯苷对糖尿病大鼠肾脏沉默信息调节因子2同源体和TGF-β_1蛋白的影响

Effect of tetrahydroxystilbene glucoside on silent mating type information regulation 2 homolog 1 and transforming growth factor-β_1 in kidney of diabetic rats

目的探讨二苯乙烯苷(TSG)对糖尿病大鼠肾脏沉默信息调节因子2(SIRT1)和转化生长因子-β1(TGF-β1)蛋白的影响。方法以链脲佐菌素腹腔注射建立糖尿病大鼠模型和高糖刺激大鼠肾系膜细胞株为研究对象,全自动生化分析仪测定生化指标,比色法检测细胞培养液中的超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的活性、丙二醛(MDA)含量的变化,四甲基偶氮唑蓝(MTT)测定肾小球系膜细胞(GMCs)增殖活性,Western印迹检测大鼠肾脏和系膜细胞中SIRT1和TGF-β1蛋白表达。结果糖尿病肾病(DN)组大鼠的24 h尿蛋白定量、肾脏肥大指数、三酰甘油(TG)、总胆固醇(TC)、血尿素氮(BUN)、血肌酐(C r)与对照组比较明显增加(P<0.01),而TSG能明显改善上述指标,并改善大鼠抗氧化应激能力。TSG能明显增加糖尿病大鼠肾脏和高糖环境下系膜细胞SIRT1蛋白表达,并抑制TGF-β1蛋白表达。结论 TSG对DN具有保护作用,其作用机制可能通过提高机体抗氧化应激能力,调节SIRT1活性,并抑制肾脏TGF-β1蛋白表达而减少DN损害。

Objective To observe the influence of tetrahydroxystilbene glucoside（TSG）on silent mating type information regulation 2 homolog 1（SIRT1） and transforming growth factor-β1（TGF-β1） in kidney of rat with diabetes.Methods Diabetes mellitus model was induced by intraperitoneal injection of streptozotocin（60 g/kg）.The serum biochemical parameters in rats were measured by automatic chemistry analyzer.The activity of superoxide dismutase（SOD） and the levels of malondialdehyde（MDA）,glutathione（GSH） in renal tissue were assayed.The proliferation activity of mesangial cells was assessed by MTT assay,the expression of SIRT1 and TGF-β1 protein examined by Western blot.Results 24 hours urinary albumin excretion（UAE）,kidney hypertrophy index,cholesterol（TC）,triacylglyceride（TG）,serum urea nitrogen（BUN）,serum creatinine in diabetic rats were increased compared with control group.TSG could improve above changes and the ability of antioxidation.TSG could increase the expression of SIRT1 in kidney of diabetic rat and mesangial cells cultured in high glucose and inhibit the expression of TGF-β1.Conclusions The protective mechanisms of TSG against DN are involved in the alleviation of oxidative stress injury and the depression of TGF-β1, partially via the activation of SIRT1.