舒拉明对高糖作用下腹膜间皮细胞转分化的影响  

Effect of suramin on the epithelial-mesenchymal transition in peritoneal mesothelial cells inducedby high concentration glucose

作　　者：马姝琛[1] 刘娜[1] 兰洋[1] 庄守纲[1] 严海东[1] 

机构地区：[1]同济大学附属东方医院肾内科,上海200120

出　　处：《中华肾脏病杂志》2013年第2期142-146,共5页Chinese Journal of Nephrology

基　　金：国家自然科学基金（81170638,81270778,81200492）

摘　　要：目的探讨舒拉明（suramin）对高糖作用下人腹膜间皮细胞（PMC）上皮细胞转分化（EMT）及转化生长因子B1（TGF-β1）分泌的影响。方法人PMC常规细胞培养、传代后用于实验。细胞分组：（1）正常对照组；（2）高糖组：不同浓度葡萄糖（Gs）（1．5％、2．5％、4．25％）分别作用于人PMC12、24、48h；（3）舒拉明组：高糖（4．25％GS）作用于人PMC，不同浓度舒拉明（25、50、100μmol／L）处理细胞48h。Western印迹方法检测细胞α-SMA、E-cadherin的蛋白表达水平。ELISA法检测细胞培养上清液中TGF-β1的含量。结果与正常对照组相比，高糖诱导PMC中α-SMA表达明显上调，E-cadherin表达明显下调，并呈浓度、时间依赖性（均P〈0．05）。高糖可促进PMC分泌TGF-β1（P〈0．05）。舒拉明可抑制高糖诱导的腹膜间皮细胞α-SMA表达上调、E-cadherin表达下调及TGF-β1分泌增加，并呈浓度依赖性（均P〈0．05）。结论高糖可诱导人PMC的EMT效应。舒拉明以浓度依赖性效应抑制人PMC的EMT，这种效应可能与舒拉明抑制人PMC的TGF-β1分泌有关，提示舒拉明可能成为治疗腹膜纤维化的潜在新型药物。Objective To explore the effect of suramin on the epithelial- mesenchymal transition （EMT） and the excretion of transforming growth factor-β1 （TGF-β1） in peritoneal mesothelial cells （PMCs） induced by high concentrations of glucose solution （GS）. Methods Cultured PMCs were divided into three groups： （1） normal control group; （2） GS-treated group： cells were treated with 1.5%, 2.5%, 4.25% GS for 12 h, 24 h, 48 h, respectively; （3） Suramin-treated group： PMCs cultured with 4.25% GS were exposed to different doses of suramin （25, 50, 100 μmol/L） for 48 h. Expression levels of α- smooth muscle actin （α-SMA） and E- cadherin were detected by Western blotting and the concentration of TGF-β1 in the culture supernatant was determined by ELISA. Results Compared with normal control group, GS-treated PMCs exhibited a time-dependent increase in the expression of α-SMA, and decrease in the expression of E-cadherin. GS also stimulated PMCs to secrete TGF-β1. In the presence of suramin, GS- induced α- SMA expression and TGF-β1 production were reduced, E-cadherin expression was increased. Conclusions Suramin can inhibit high glucose-induced EMT of PMCs by down-regulating the expression of TGF-β1. Suramin may be a novel therapeutic agent for the treatment of peritoneal fibrosis.

关 键 词：细胞转分化 舒拉明 转化生长因子β1 腹膜间皮细胞 

分 类 号：R692[医药卫生—泌尿科学]