中文摘要：

目的：肝星形细胞（hepatic stellate cells,HSCs）是参与肝纤维化和肝硬化发展过程的主要细胞。在肝纤维化过程中,肝星形细胞增殖并发生表型转化,从静止状态向肌纤维母细胞样转化。后者的归宿可为凋亡,也可重归静止状态。目前转化肌纤维母细胞样细胞的凋亡机制尚未明确。本文研究细胞外信号调节激酶（extracellular signal-regulated kinases,ERKs）磷酸化状态对十字孢碱诱导HSCs凋亡的影响。方法：采用Western印迹和流式细胞术检测4种肝星形细胞株（CFSC-8B,-2G,-3H和-5H）的ERKs表达水平和细胞凋亡状态。结果：4种肝星形细胞株各具有形态特异性,并与其内α-SMA表达水平相符,其中CFSC-8B细胞株α-SMA表达水平为最高。虽然ERK1/2总蛋白表达水平在4种细胞株相似,但磷酸化ERK1/2在CFSC-8B和CFSC-2G两个细胞株中表达明显高于CFSC-3H和CFSC-5H细胞株。进一步采用CFSC-8B细胞（ERK1/2高磷酸化水平）和CFSC-5H细胞（ERK1/2低磷酸化水平）,通过十字孢碱诱导细胞凋亡。结果显示CFSC-8B细胞对十字孢碱诱导的细胞凋亡敏感性明显增加。同时,十字孢碱还可进一步增加这2株细胞内ERK1/2的磷酸化程度。结论：HSCs中ERK1/2的磷酸化程度决定细胞对十字孢碱所致细胞凋亡的敏感性。

英文摘要：

Objective： Hepatic stellate cells（HSCs） are the principal cells responsible for the development of hepatic fibrosis and cirrhosis.During the fibrotic process,HSCs undergo proliferation and transdifferentiation from a quiescent to myofibroblast-like phenotype.The fate of myofibroblast-like HSCs includes apoptosis or reversion back to a quiescent phenotype.The mechanisms involved in the apoptotic process of HSCs have yet to be determined.The purpose of the present study is to determine the effects of extracellular signal-regulated kinases（ERKs） phosphorylation on the apoptosis of HSCs induced by staurosporine.Methods： We used Western blot and flow cytometry to detect the expression level of ERK and cell apoptosis status in four rat hepatic stellate cell lines（CFSC-8B,-2G,-3H and-5H）.Results： Each hepatic stellate cell line had a distinct morphology consistent with their expression level of α-SMA and that CFSC-8B cells had the highest α-SMA expression.Although all four cell types expressed similar levels of ERK1/2,phosphorylation levels were significantly higher in CFSC-8B and CFSC-2G than in CFSC-3H and CFSC-5H cells.When CFSC-8B cells（high ERK1/2 phosphorylation） and CFSC-5H cells（low ERK1/2 phosphorylation） were employed to examine staurosporine-induced apoptosis,CFSC-8B cells were significantly more sensitive.Staurosporine further increased ERK1/2 phosphorylation in both cell lines.Conclusion： ERK1/2 phosphorylation in HSCs determines the sensitivity of HSCs to staurosporine-induced apoptosis.