内皮素-1对活化肝星状细胞增殖及钙离子影响的调控机制研究  

Effects of endothelin-1 on proliferation and changes of Ca^(2+) in activat ed hepatic stellate cells

作　　者：姚希贤[1] 姚冬梅[1] 房红梅[1] 杨川杰[1] 张晓岚[1] 刘丽[1] 苏素文[2] 王川[2] 

机构地区：[1]河北医科大学第二医院消化内科,石家庄050000 [2]河北医科大学基础医学院药理教研室

出　　处：《中华消化杂志》2004年第11期659-662,共4页Chinese Journal of Digestion

摘　　要：目的　探讨内皮素(ET -1)对活化的肝星状细胞(HSCs)细胞外信号调节激酶 1(ERK1)表达、细胞周期及细胞内Ca2 + 影响。方法　采用Western印迹观察不同浓度ET -1对HSCsERK1的表达,采用流式细胞术观察ET -1对细胞周期的影响,并借助激光共聚焦显微镜技术观察ET- 1对HSCsCa2 +浓度变化和细胞面积的影响。结果　ET -1可剂量依赖性地抑制HSCsERK1的表达,最高浓度ET -1可显著抑制ERK1表达,同对照组相比下降(10 .91±3.36 ) % (P <0 .0 5 ) ,还可抑制HSCsDNA合成,使增殖指数由(32 .6 3±0 .36 ) %下降至(2 4 .72±0 .12 ) % (P <0 .0 1) ,同时ET- 1可引起HSCs [Ca2 + ]i的升高及细胞面积的减少(P <0 .0 5 )。结论　ET- 1对HSCs发挥着促进HSCs收缩与抑制其增殖的双重作用,所以应用药物治疗慢性肝病既要注意抑制ET的收缩效应同时又要兼顾对其本身具有的抑制增殖的双重作用。Objective To elucidate the effects of endothelin-1(ET-1) on expression of extra-regulated kinase 1(ERK 1), cell cycle and changes of Ca 2+ in activated hepatic stellate cells (HSCs). Methods Effects of different concentra tions of ET-1 on ERK 1 expression were determined by Western blotting. Effects of ET- 1 on cell cycle were observed by flow cytometry(FCM) analysis. Effects of ET-1 on changes of calcium concentration and cell area were observed by laser scanning confocal microscopy (LSCM). Results ET-1 could inhibit the expression of ERK 1 i n a dose-dependent manner, compared with the control, the expression of ERK 1 in E T-1 highest concentration group decreased 10.91%±3.36% (P<0.05).ET-1 cou l d inhibit DNA synthesis of HSCs, the proliferation index (PI) of HSCs decreased from 32.63%±0.36% to 24.72% ±0.12% (P<0.01). Meanwhile, ET-1 could also el icit the elevation of [Ca 2+]i and area reduction of HSCs (P<0.05). Conclusions ET-1 has the characters of both eliciting contraction and inhibiting proliferation of HSCs, so the attention should be paid to the dual roles when we study the drugs of ant i-fibrosis.

关 键 词：ET-1 HSC ERK 表达 观察 抑制 肝星状细胞增殖 调控机制 细胞内CA^2+ 钙离子 

分 类 号：R575.2[医药卫生—消化系统]