氯沙坦抑制环孢素A诱导的系膜细胞增生和细胞外基质形成  

Effect of cyclosporine A and losartan on the proliferation and secretion of extracelular matrix in mesangial cells

作　　者：张树俭[1] 尚明花[1] 姚建[1] 刘军[1] 唐知还[1] 于青[1] 

机构地区：[1]上海市交通大学附属第一人民医院肾内科,上海200080

出　　处：《肾脏病与透析肾移植杂志》2003年第1期24-27,共4页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的 :观察免疫抑制剂环孢素A(CsA)对系膜细胞 (MC)增生及细胞外基质 (ECM)分泌的影响以及氯沙坦的干预作用 ,初步探讨环孢素致肾小球硬化的机制。　 方法 :体外培养大鼠肾小球MC ,用氚标胸腺嘧啶核苷(3 H TdR)掺入法测定CsA对MC增生的影响 ,用酶联免疫吸附实验 (ELISA)测定细胞上清液中转化生长因子 β1(TGF β1)及ECM成份纤维连接蛋白 (fibronectin ,Fn)的分泌 ,用逆转录 聚合酶链反应 (RT PCR)方法测定TGF β1、Ⅰ型前胶原、基质金属蛋白酶 2 (MMP 2 )的基因表达。　 结果 :CsA对MC的增生有明显的抑制作用 ,并呈现时间和剂量依赖效应 ,氯沙坦对细胞的增生无明显作用 ;环孢素能明显促进TGF β1及Fn的分泌 ,并能促进TGF β1、Ⅰ型前胶原mRNA的表达 ,下调MMP 2mRNA的表达 ,氯沙坦能下调环孢素诱导的TGF β1及Fn的表达。　 结论 :环孢素影响MC增生和ECM分泌从而引起肾小球硬化 ,肾素 血管紧张素Objective:To evaluate the effects of cyclosporine (CsA) and losartan on the proliferation and extracellular matrix (CEM) production in cultured mesangial cells,and investigate the mechanisms of CsA-induced glomerulosclerosis. The cell proliferation was measured by 3H-TdR incorporation.The protein synthesis of transforming growth factor beta(TGF-β1) and fibronectin were detected by enzyme-linked immunoadsorbent assay (ELISA).The expression of TGF-β1,procollagen α1(Ⅰ) and matrix metalloproteinase-2(MMP-2) mRNA were evaluated by semi-quantitive reverse transcription polymerase chain response (RT-PCR). CsA inhibited the proliferation of mesangial cells in dose and time dependent way,while losartan had no effects on it.CsA stimulated the protein secretion of TGF-β1 and fibronectin in a dose dependent manner,however,losartan down-regulated those protein production induced by CsA.CsA also stimulated the expression of TGF-β1,procollagen α1(Ⅰ) and inhibited MMP-2 mRNA expression and losatan partly reversed those effects. The effect of CsA on cell proliferation and production of ECM may play an important role in the pathogensis of CsA induced glomerulosclerosis.

关 键 词：环孢素A 免疫抑制剂 系膜细胞 细胞外基质 氯沙坦 肾小球硬化 

分 类 号：R699[医药卫生—泌尿科学]