转化生长因子-β_1/Smad 2信号通路在他克莫司抑制人肾小球系膜细胞增殖中的作用  

The effect of TGF-β_1/smad 2 in tacrolimus inhibition on the proliferation of human glomerular mesangtal cells

作　　者：杨伟鹏 罗琰琨[2] 原成英[2] 周晓霜[2] Yang Weipeng;Luo Yankun;Yuan Chengying;Zhou Xiaoshuang(Department of Nephrology,Yuncheng Municipal Central Hospital,Shanxi 044000,China)

机构地区：[1]山西省运城市中心医院肾内科,044000 [2]山西省人民医院肾内科

出　　处：《中国药物与临床》2018年第5期685-687,共3页Chinese Remedies & Clinics

基　　金：山西省青年科技研究基金面上青年基金(201701D221263);山西省人民医院博士科研启动基金(b201622)

摘　　要：目的探讨他克莫司(TAC)对人肾小球系膜细胞细胞周期的作用及其抑制人肾小球系膜细胞周期性增殖的机制。方法 5μmol/L的TAC分别培养人肾小球系膜细胞24、48、72 h,用四甲基偶氮唑盐(MTT)法测细胞增殖,流式细胞仪测细胞周期,流式细胞仪测细胞凋亡。进一步将人肾小球系膜细胞分为正常对照组(CTL组)、转化生长因子-β1组(TGF-β_1组)、TAC组、TGF-β_1+TAC组,采用蛋白质印迹法检测各组Smad 2蛋白的表达水平。结果 5μmol/L TAC作用于人肾小球系膜细胞48 h,细胞在S期的比例明显下降了(P<0.05),在G0/G1期的百分比增加(P<0.05)。与CTL组相比,TGF-β_1组Smad 2蛋白表达水平显著上调(P<0.01);与CTL组相比,TAC组Smad 2蛋白质表达水平明显下降(P<0.01);与TGF-β_1组相比,TGF-β_1+TAC组Smad 2蛋白表达水平明显降低(P<0.01)。结论 TAC可能通过影响TGF-β_1/Smad 2信号通路阻断人肾小球系膜细胞由G1期进入S期而抑制其增值。Objective To investigate the effect of tacrolimus（TAC） on the cell cycle of human glomerular mesangial cells（HMCs） and the mechanism of its inhibition on the periodic proliferation of HMCs. Methods The HMCs were cultured with 5 μmol/L TAC for 24 h, 48 h and 72 h, respectively. The cell proliferation was measured by MTT assay. The cell cycle and apoptosis was determined by flow cytometry, respectively. The HMCs were further divided into the normal control group（CTL group）, transforming growth factor-β1 group（TGF-β1 group）, TAC group,and TGF-β1＋ TAC group. The protein expression level of Smad 2 in each group was determined by Western blotting.Results At 48 h after treating HMCs with 5 μmol/L TAC, the proportion of cells in S phase decreased significantly（P〈0.05）, and the percentage in G0/G1 phase increased（P〈0.05）. Compared with the CTL group, the Smad 2 protein expression level was significantly up-regulated in the TGF-β1 group（P〈0.01）. Compared with the CTL group, the Smad 2 protein expression level in the TAC group significantly decreased（P〈0.01）. Compared with the TGF-β1 group,the Smad 2 protein expression level in the TGF-β1＋TAC group significantly decreased（P〈0.01）. Conclusion TAC may block the progression of HMCs from G1 phase to S phase and inhibit the proliferation by affecting TGF-β1/Smad2 signaling pathway.

关 键 词：肾小球系膜细胞 细胞增殖 他克莫司 

分 类 号：R692.6[医药卫生—泌尿科学]