CAJ | 학술논문

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β1 (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PMC 12、24、48 h；(3)舒拉明组:高糖(4.25％ GS)作用于人PMC,不同浓度舒拉明(25、50、100 μmol/L)处理细胞48 h.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.
목적 탐토서랍명(suramin)대고당작용하인복막간피세포(PMC)상피세포전분화(EMT)급전화생장인자β1 (TGF-β1)분비적영향.방법 인PMC상규세포배양、전대후용우실험.세포분조:(1)정상대조조；(2)고당조:불동농도포도당(GS)(1.5％、2.5％、4.25％)분별작용우인PMC 12、24、48 h；(3)서랍명조:고당(4.25％ GS)작용우인PMC,불동농도서랍명(25、50、100 μmol/L)처리세포48 h.Western인적방법검측세포α-SMA、E-cadherin적단백표체수평.ELISA법검측세포배양상청액중TGF-β1적함량.결과 여정상대조조상비,고당유도PMC중α-SMA표체명현상조,E-cadherin표체명현하조,병정농도、시간의뢰성(균P＜ 0.05).고당가촉진PMC분비TGF-β1(P＜0.05).서랍명가억제고당유도적복막간피세포α-SMA표체상조、E-cadherin표체하조급TGF-β1분비증가,병정농도의뢰성(균P＜0.05).결론 고당가유도인PMC적EMT효응.서랍명이농도의뢰성효응억제인PMC적EMT,저충효응가능여서랍명억제인PMC적TGF-β1분비유관,제시서랍명가능성위치료복막섬유화적잠재신형약물.
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.