替米沙坦对转化生长因子胞内信号蛋白Smad2/3在糖尿病大鼠肾脏表达的影响及意义

摘要

目的 研究替米沙坦对转化生长因子β1(TGF-β1)胞内信号蛋白Smad2/3在糖尿病大鼠肾脏表达的影响及意义.方法 用链脲佐菌素制备糖尿病大鼠模型,采用免疫组织化学、蛋白质印迹法及反转录-聚合酶链反应(RT-PCR)检测糖尿病大鼠TGF-β1和Smad2/3在肾组织中的表达水平.结果 治疗前,与对照组比,其余组别的血糖(BG)、尿肌酐(Ucr)、内生肌酐清除率(Ccr)和24 h尿蛋白(UP)均明显增高(P<0.05),治疗后,与糖尿病4周比,糖尿病8周的BG、Ucr、Ccr和24 h U P略有增高.与糖尿病4周和糖尿病8周比,相应替米沙坦干预组的BG、Ucr、Ccr和24 h UP显著降低(P<0.05).免疫组织化学和蛋白质印迹法检验显示,与对照组比,糖尿病4周组和8周组的TGF-β1和Smad2/3在肾组织的表达均明显增高(P<0.05),与糖尿病4周和8周组比,对应替米沙坦干预组的TGF-β1和Smad2/3表达均明显降低(P<0.05).RT-PCR检测显示,与对照组比,糖尿病4周组和8周组的TGF-β1和Smad2/3mRNA表达均明细增高(P<0.05),与糖尿病4周和8周组比,对应干预组的TGF-β1和Smad2/3 mRNA表达均明显降低(P<0.05).结论 替米沙坦可降低糖尿病大鼠肾脏TGF-β1胞内信号蛋白Smad2/3的表达.%Objective To investigate the effect of telmisartan on the expression of transforming factor β1 (TGF-β1 ) intracellular signaling protein Smad2/3 in the kidney of diabetic rats .Methods Streptozotocin was used to made diabetic rats .The expression of TGF-β1 and Smad2/3 in renal tissue were detected by immunohistochem-istry ,western blot and RT-PCR .Results Before treatment ,compared with control group , the blood glucose (BG) ,urine creatinine(Ucr) ,endogenous creatinine clearance rate(Ccr) and 24 hour urine protein(24 h UP) had increased in other 4 groups( P <0 .05) .After treatment ,the BG ,Ucr ,Ccr and 24 h UP had increased in the 8 weeks diabetes mellitus group ,compared with 4 weeks diabetes mellitus group .Compared with 4 weeks and 8 weeks diabetes mellitus groups ,the BG ,Ucr ,Ccr and 24 h UP had decreased in 4 weeks and 8 weeks diabetes mellitus+ telmisartan groups( P<0 .05) .The immunohistochemistry and western blot showed that the expression of TGF-β1 and Smad2/3 had increased in 4 weeks and 8 weeks diabetes mellitus groups ,compared with the control groups( P <0 .05) .Compared with 4 weeks and 8 weeks diabetes mellitus groups ,the expression of TGF-β1 and Smad2/3 had decreased in 4 weeks and 8 weeks diabetes mellitus + telmisartan groups ( P < 0 .05) .RT-PCR showed that expression of TGF-β1 mRNA and Smad2/3 mRNA had increased in 4 weeks and 8 weeks diabetes mellitus groups ,compared with the control group s ( P <0 .05) .Compared with 4 weeks and 8 weeks diabetes mellitus groups ,the expression of TGF-β1 mRNA and Smad2/3 mRNA had decreased in 4 weeks and 8 weeks dia-betes mellitus+ telmisartan groups( P <0 .05) .Conclusion Telmisartan can reduce the expression of Smad2/3 protein in the TGF-β1 cells of kidney in diabetic rats .