缬沙坦联合丹参对糖尿病大鼠肾脏协同保护作用及机制

Superior Renoprotective Effects of the Combination of Valsartan with Salvia Miltiorrhiza and its Mechanism in Diabetic Rats

目的探讨缬沙坦联合丹参对糖尿病大鼠肾脏协同保护作用及机制。方法建立链脲佐菌素(STZ)诱导的单侧肾切除糖尿病大鼠模型,随机分为5组:正常对照组(NC)、模型组(DM)、缬沙坦组(DM+V)、丹参组(DM+S)及缬沙坦与丹参联合给药组(DM+V+S),8周后观察血糖、糖化血红蛋白(HbAlc)、内生肌酐清除率(Ccr)、尿白蛋白排泄率(UAE)、尿β2微球蛋白排泄率(β2-MG)等变化。放射免疫法检测血浆、尿液及肾组织中内皮素(ET-1)的水平,ELISA法检测血清、尿液中转化生长因子β1(TGF-β1)水平。结果①模型组及各给药组大鼠血糖、HbAlc、Ccr、UAE、β2-MG,血、尿中ET-1、TGF-β1及肾组织中ET-1水平均明显高于对照组(P均<0.01)。②模型组血、尿中ET-1、TGF-β1及肾组织中ET-1水平明显高于各给药组(P<0.05)。③各给药组均可降低血、尿中ET-1、TGF-β1及肾组织中ET-1水平及Ccr、UAE、β2-MG(P均<0.01),联合组优于单给药组(P<0.05,P<0.01)。结论缬沙坦联合丹参对糖尿病肾脏的保护作用优于单药治疗。其机制部分与其抑制ET-1、TGF-β1等细胞因子的表达有关。

Objective To assess superior renoprotective effects of the combination of valsartan with salvia miltiorrhiza and its mechanism in diabetic rats. Methods Diabetes was induced by injection of streptozotocin after uninephrectomy. Rats were randomly separated into five groups： control, diabetes, diabetes treated with valsartan, diabetes treated with salvia miltiorrhiza, and diabetes treated with combined valsartan and salvia miltiorrhiza. Plasma glucose, glycosylated hemoglobin （HbAlc）, urinary albumin excretion （UAE）, urinary β2-MG excretion and creatinine clearance （Ccr） was observed by light microscopy after 8 weeks. Expression of SET-1, UET-1, RET-1 was examined by radioimmunity technique. Expression of STGF - β1、 UTGF -β1 was examined by enzyme linked immunosorbent assay （ELISA）. Results ①Plasma glucose, HbA1c、Ccr、UAE、β 2-MG and the SET-1、UET-1、RET-1、STGF- β1、UTGF-β1 were significantly higher in the diabetes, diabetes treated with valsartan and （or） salvia miltiorrhiza than those in the control group （P 〈 0.01）. ②The SET-1、UET-1、RET-1、STGF-β1、UTGF-β1 in diabetes group were significantly higher than those in the diabetes treated with valsartan and （or） salvia miltiorrhiza （P 〈 0.05）. ③Either diabetes treated group can degraded the expression of SET-1、UET-1、RET-1、STGF- β 1、UTGF-β1 and Ccr、UAE、β 2-MG, combination therapy was better than monotherapies （P 〈 0.05, P 〈 0.01）. Conclusion The combination of valsartan with salvia miltiorrhiza confers superiority over monotherapies on renoprotection, whose mechanism may be at least partly related with suppressing the over expressions of ET- 1、TGF - β 1 in renal cortex.