糖肾平对高糖+LPS刺激足细胞TGF-β1/Smad7信号转导通路影响的研究

摘要

Objective:To observe the influence of the capsule of Tang shen ping on LPS - induced TGF - β1/Smad7 signal transduction of podocytes under high glucose conditions, and explore its possible mechanism. Methods: Build the growth model of podocyte induced by LPS in high glucose conditions, and divide them into 8 groups: control group;high glucose group;high glucose plus LPS group;Irbesartan group;low - dose group of Tangshenping capsule; moderate dose group of Tangshenping capsule; high -dose group of Tangshenping capsule; inhibitor group. Detect podocyte TGF - β1, Smad7, and NF - ΚB protein expression of each group by Western - blotting the molecular biology level. Results: Compared with the control group, the expression of podocyte TGF - β1、NF - ΚB protein increased definitely ( P <0. 01 ), Smad7 protein decreased definitely ( P <0. 01 ) in the high glucose group and high glucose plus LPS groups. In the inhibitor group podocyte TGF - β1 , NF - ΚB protein expression were significantly lower ( P < 0. 01 ), while Smad7 protein expression was significantly higher ( P <0. 01 ) than the high glucose group and high glucose plus LPS groups. Compared with the high glucose group and high glucose plus LPS groups, the expression of podocyte TGF - Β1 decreased ( P < 0. 05 ), NF - ΚB protein decreased definitely ( P < 0. 01 ), and Smad7 protein increased definitely ( P < 0.01 ) in the Irbesartan group; In the high, moderate, and low dose groups of Tangshenping capsule, podocyte TGF - β1 protein expression decreased ( P < 0. 05 ); podocyte NF - ΚB protein expression decreased definitely ( P < 0.01 )in the high - dose group and decreased ( P < 0. 05 ) in both moderate and low - dose groups of Tangshenping capsule; Smad7 protein increase definitely (P<0.01 ) in the high and low dose groups of Tangshenping capsule. Conclusion: Tangshenping capsule can reduce podocyte TGF - β1、NF - ΚB protein expression and increase Smad7 protein expression, reducing podocyte apoptosis by intervention of TGF - Β1、 - smad7 - NF - ΚB signaling pathways. This mechanism may be considered as a means of prevention and treatment for diabetic nephropathy.%目的:观察糖肾平胶囊对高糖环境下脂多糖(lipopolysaccharide,LPS)刺激足细胞转化生长因子-β1(transforming growth factor-β1,TGF-β1)/Smad7信号转导通路的影响,并探讨其作用机制.方法:以高糖、LPS刺激足细胞建立模型,分为正常组、高糖组、高糖+LPS组、厄贝沙坦组、糖肾平小、中、大剂量组和抑制剂组.采用Western-Blotting方法检测足细胞中TGF-β1、Smad7、核因子-κB(nuclear factor-kappaB,NF-κB)的表达.结果:与正常组比,高糖组和高糖+LPS组足细胞TGF-β1、NF-κB表达明显升高(P<0.01),Smad7表达明显降低(P<0.01);抑制剂组足细胞TGF-β1、NF-κB蛋白表达比高糖组和高糖+LPS组均明显降低(P<0.01),Smad7蛋白表达明显升高(P<0.01),厄贝沙坦组TGF-β1蛋白表达比高糖组和高糖+LPS组降低(P<0.05),NF-κB蛋白表达明显降低(P<0.01),Smad7蛋白表达明显升高(P<0.01),糖肾平胶囊大、中、小剂量组足细胞中TGF-β1蛋白表达比高糖组和高糖+LPS组均降低(P<0.05),大剂量组足细胞NF-κB蛋白表达比高糖组和高糖+LPS组均明显降低(P<0.01),中、小剂量组足细胞NF-κB蛋白表达比高糖组和高糖+LPS组均降低(P<0.05),糖肾平胶囊大、小剂量组Smad7蛋白表达比高糖组和高糖+LPS组均明显升高(P<0.01).结论:糖肾平能够降低足细胞TGF-β1、NF-κB蛋白的表达,增加Smad7蛋白表达,通过干预TGF-β1-smad7-NF-κB信号转导通路减少糖尿病肾病足细胞凋亡,可能是其防治糖尿病肾病的作用机制之一.