细胞外信号调节激酶调控乙醛对肝星状细胞的影响

Effects of extracellular signal-regulated kinase on cell cycle and functions of rat cultured hepatic stellate cells stimulated by acetaldehyde

目的 观察PD980 5 9(特异性丝裂原细胞外信号反应激酶阻断剂 )调控乙醛刺激大鼠肝星状细胞 (HSC)周期 ,影响细胞增殖、Ⅰ型胶原蛋白分泌及转化生长因子 (TGF) β1mRNA表达。方法 不同浓度PD980 5 9对乙醛刺激的HSC进行处理 ;流式细胞仪检测细胞周期 ,MTT法检测细胞增殖变化 ,ELISA法检测HSC内Ⅰ型胶原蛋白分泌 ,RT PCR法检测HSC内TGFβ1mRNA表达。结果 PD980 5 9能剂量依赖性地影响乙醛刺激的HSC周期 ,使G0 /G1期细胞百分比增高 ,S期细胞减少 ,从而抑制乙醛刺激的HSC增殖、HSC内Ⅰ型胶原蛋白分泌及TGFβ1mRNA表达。

Objective To investigate the effects of PD98059, the specific blocking agent of mitogen extracellular signal responsive kinase, on the cell cycle, cell proliferation, type Ⅰ collagen's secretion and transforming growth factor(TGF)β 1mRNA expression of rat hepatic stellate cells (HSC) stimulated by acetaldehyde. Methods Rat HSC stimulated by acetaldehyde were incubated with different concentration of PD98059. Cell cycle was analysed by flow cytometry. Cell proliferation was assessed by MTT colorimetric assay. Type Ⅰcollagen of culture medium was detected by enzyme linked immunoadsordent assay (ELISA). TGFβ 1mRNA expression were examined by RT PCR. Results 20,50,100 μmol/L PD98059 could significantly inhibit proliferation and induced G0/G1 phase arrest of HSC stimulated by acetaldehyde in a does dependent manner. 50,100 μmol/L PD98059 could markedly inhibit type Ⅰcollagen's secretion and TGFβ 1mRNA expression of HSC stimulated by acetaldehyde. Conclusion The extracellular signal regulated kinase signal transduction passway regulates the cell proliferation, type Ⅰcollagen's secretion and TGFβ 1mRNA expression of rat HSC stimulated by acetaldehyde,which might be partly related to its regulative effect on the cell cycle.