去甲斑蝥素对TGF-β_1诱导的人近端肾小管细胞上皮间质转分化以及转录因子Snail1表达的影响  

Effect of Norcantharidin on Inhibition of Tubular Epithelial-Mesenchymal Transition and Downregulation of Snail1 in HK-2 Induced by TGF-β_1

作　　者：刘伏友[1] 孙岩[1,2] 孙林[1] 凌光辉[1] 李瑛[1] 刘健[2] 袁曙光[1] 刘映红[1] 张东山[1] 夏运成[1] 

机构地区：[1]中南大学湘雅二医院肾内科,长沙410011 [2]新疆医科大学第一附属医院肾内科,乌鲁木齐830011

出　　处：《中国中西医结合肾病杂志》2009年第11期952-957,共6页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家中医药管理局中医药科学技术研究基金资助项目(No.06-07ZP33);湖南省卫生厅中医药科研基金资助项目(No.6103);湖南省科技计划资助项目(No.2007SK3040)

摘　　要：目的:探讨去甲斑蝥素对体外人源性肾小管细胞株(HK-2)上皮间质转分化以及转录因子Snail1的影响。方法:常规培养HK-2细胞,分为对照组、TGF-β1组、去甲斑蝥素组(NCTD组)。对照组为无血清DMEM培养,TGF-β1组为TGF-β15ng/ml诱导,NCTD组为不同浓度NCTD(0.5、1.0、2.5μg/ml)与TGF-β1(5ng/ml)共同作用,各组作用时间48h。采用RT-PCR、Western blot分别检测α-SMA、E-cadherin与Snail1表达水平的变化。结果:与对照组相比,TGF-β1组α-SMA mRNA和蛋白表达上调(P<0.05),E-cadherin mRNA和蛋白表达下调(P<0.05);与TGF-β1组相比,NCTD干预组α-SMA mRNA和蛋白表达下调(P<0.05),而E-cadherin mRNA和蛋白表达上调(P<0.05),且均呈剂量依赖性。与对照组相比,TGF-β1组Snail1 mRNA和蛋白表达上调(P<0.05);与TGF-β1组比较,NCTD干预组Snail1 mRNA和蛋白表达下调(P<0.05),具有一定的剂量依赖关系。结论:去甲斑蝥素具有抑制肾小管上皮细胞EMT的作用,该作用可能与下调转录因子Snail1的表达有关。Objective：To investigate the effect of norcantharidin on EMT and the expression of transcription factor Snail1 in HK-2 cells induced by TGF-β1.Methods：Human proximal tubular epithelial cells （HK-2） were divided into three groups：the control group （only FBS-free DMEM）,the TGF-β1 group （treated with TGF-β1 5 ng/ml） and the NCTD group（treated with TGF-β1 5 ng/ml and norcantharidin at different dose）.The expressions of α-SMA,E-cadherin and Snail1 in HK-2 cells were determined by RT-PCR and Western blot,respectively.Results：The expression of α-SMA increased in HK-2 induced by TGF-β1,while that of NCTD group treated by NCTD （0.5,1.0,2.5）μg/ml was dramatically inhibited in a dose-dependent manner.The expression of E-cadherin in HK-2 induced by TGF-β1 partly reversed by NCTD （0.5,1.0,2.5）μg/ml） in a dose-dependent manner.The expression of Snail1 in HK-2 induced by TGF-β1 （5 ng/ml） was suppressed by NCTD （0.5,1.0,2.5）μg/ml in a dose-dependent manner.Conclusion：NCTD may inhibit EMT of tubular cells induced by TGF-β1,which may associate with the down-regulation of Snail1 expression.

关 键 词：去甲斑蝥素 上皮间质转分化 转化生长因子-Β1 SNAIL1 

分 类 号：R692[医药卫生—泌尿科学]