普罗布考对糖尿病肾病大鼠TGF-β1/Samd6/BMP7信号通路的影响及其意义

Effect of probucol on TGF-β1/Samd6/BMP7 signal pathway in diabetic kidney disease rats

目的:探讨普罗布考对糖尿病肾病(DKD)大鼠转化生长因子-β1/Samd6/骨形成蛋白7(TGF-β1/Samd6/BMP7)信号通路的影响及其意义。方法:选取40只DKD大鼠,随机分为DKD组和普罗布考组各20只,另取健康SD大鼠20只为对照组,DKD组和对照组每日予生理盐水0.2ml·kg^-1灌胃,普罗布考组每日予普罗布考50mg·kg-1灌胃,均连续给药12周。给药前后分别检测空腹血糖(BG)、尿肌酐(Ucr)、内生肌酐清除率(Ccr)、24h尿蛋白(24hUP)以及治疗后肾组织TGF-β1、Samd6、BMP7蛋白和mRNA表达。结果:治疗后,普罗布考组BG、Ucr、Ccr、24hUP以及TGF-β1蛋白和mRNA表达均显著降低(P<0.05),Samd6、BMP7蛋白和mRNA表达显著增高(P<0.05),大鼠肾脏的病理表现介于正常组和DKD组之间。结论:普罗布考可上调Samd6、BMP7蛋白和mRNA表达,下调TGF-β1蛋白和mRNA的表达,通过影响TGF-β1/Samd6/BMP7信号通路的转导而减轻肾间质纤维化,延缓DKD进展。

Objective: To investigate the effect and significance of probucol on transforming growth factor -β1/Samd6/bone morphogenetic protein - 7(TGF -β1/Samd6/BMP7) signal pathway in diabetic kidney disease(DKD) rats. Methods: Forty DKD rats were randomly divided into DKD group and probucol group with 20 in each group,and 20 healthy SD rats were served as control group. The control and DKD groups were given normal saline ,while the probucol group was given probucol. All the groups were treated for 12 weeks. Blood glucose(BG),urine creatinine(Ucr),endogenous creatinine clearance rate(Ccr) and 24 h urine protein(UP) were measured before and after treatment. The expression of protein and mRNA of the TGF -β1,Samd6 and BMP7 were recorded after treat - ment . Results: After treatment,the levels of BG,Ucr,Ccr,24 h UP and TGF -β1 were decreased,and the Samd6 and BMP7 were increased in the DKD group( P <0.05). The renal pathological changes were between the control and the DKD group after treatment. Conclusion: Probucol can inhibit the TGF -β1 protein and mRNA signal transduction pathway by increasing the expression of Samd6 and BMP7 protein and mRNA. Probucol can reduce renal interstitial fibrosis and delay DKD progress by affecting the expression of TGF -β1/Samd6/BMP7 signal pathway.