ERK1/2信号通路在青蒿琥酯抑制PDGF-BB诱导HSC细胞增殖中的作用

ERK1/2 signal transduction pathway in anti-proliferation effect of PDGF-BB on HSC cells treated with Artesunate

目的:观察青蒿琥酯(Artesunate,Art)对血小板衍生生长因子-BB(platelet derived growthfactor-BB,PDGF-BB)刺激大鼠肝星状细胞(he-patic stellate cell,HSC)增殖,磷酸化细胞外信号调节蛋白激酶1/2(phosphorylated extracellularsignal regulated kinase 1/2,p-ERK1/2)表达的影响,探讨Art抗肝纤维化的分子机制。方法:实验分为对照组、PDGF-BB组、PDGF-BB+Art组和PDGF-BB+PD98059组。以PDGF-BB诱导HSC增殖,再分别加入不同浓度的Art和ERK1/2抑制剂PD98059。CCK-8法检测各组HSC细胞的增殖情况,ELISA法测定细胞上清液中Ⅰ型胶原的含量,免疫印迹(Western blot-ting)法检测各组细胞ERK1/2的表达及活化情况。结果:PDGF-BB可诱导HSC细胞增殖,p-ERK1/2表达增高,而PDGF-BB+Art组、PDGF-BB+PD98059组HSCⅠ型胶原的含量及p-ERK1/2活性均降低。结论:ERK1/2参与了PDGF-BB诱导HSC细胞增殖的作用,Art抗PDGF-BB所诱导的HSC细胞增殖作用与其抑制ERK1/2的活化有关。

AIM： To investigate the anti-proliferation effect of Artesunate and phosphorylated extracellular signal-regulated kinase1/2 expression in rat hepatic stellate cell stimulated byplatelet derived growth factor-BB,and to elucidate the molecular mechanism of Artesunate against hepatic fibrosis. METHODS： HSC cells were treated with PDGF-BB to induce cell proliferation.Artesunate and PD98059 were added respectively in order to study the relationship between the activity of ERK1/2 and proliferation of HSC cells.The cells were divided into control group,PDGF-BB group,PDGF-BB plus Artesunate group,PDGF-BB plus PD98059 group.The proliferation rates of HSC cells with different treatments were detected by CCK-8.Collagen typeⅠsynthesis was detected by ELISA.Activities of ERK1/2 in HSC cells were determined by Western blotting.RESULTS：PDGF-BB increased the proliferation rate and activity of ERK1/2 in HSC cells.PDGF-BB ＋ Art or PDGF-BB ＋PD98059 decreased the proliferation rate of HSC cells and activity of ERK1/2 in HSC cells.CONCLUSION： The activity of ERK1/2 is involved in the effect of PDGF-BB on HSC cells.Anti-proliferation effect of Artesunate on HSC cells affected by PDGF-BB is related to the decrease in the activity of ERK1/2.