索拉菲尼对肝星状细胞活性及活化的影响

摘要

目的：研究索拉菲尼对肝星状细胞（ HSC ）活性及活化的影响及作用机制。方法：分别将1、2、5、10μmol/L索拉菲尼培养液作用于LX2细胞，通过MTT检测观察不同浓度索拉菲尼对LX2细胞增殖的影响，应用免疫细胞化学染色法检测LX2细胞α-SMA的表达，ELISA法检测LX2细胞上清中PDGF-BB和TGF-β1水平变化， Western blot法检测各组LX2细胞PDGF信号通路各蛋白表达情况。结果：各组、各时间点LX2细胞增殖抑制率比较，差异均有统计学意义（F组间＝1045．010，F时间＝279．740，F交互＝20．130，P均＜0．001）。各组α-SMA的表达情况比较，差异有统计学意义（H＝35．630，P＜0．001）。各组、各时间点PDGF-BB和TGF-β1水平比较，差异均有统计学意义（ P均＜0．05）。实验组与对照组中ERK1、ERK2、AKT的表达基本相同，但在10μmol/L索拉菲尼干预后，各磷酸化蛋白表达降低。结论：索拉菲尼可抑制HSC的增殖及活化。%To investigate effects and mechanisms of sorafenib on hepatic stellate cell ( HSC) viability and acti-vation.Methods:LX2 cells were cultured with 1,2,5,10 μmol/L sorfenib and detected with MTT assay at different time respectively .Expression of α-SMA was measured immunocytochemically in LX 2 cells treated with different concentrations of sorafenib.Changes in PDGF-BB and TGF-β1 concentrations were detected in LX2 supernatant using ELISA .Expression of ERK1 , ERK2 and AKT signaling pathways was measured using Western blot assay .Results:After treatment with various concentrations of sorafenib for different times , the LX2 inhibition rate increased gradually ( Fgroup =1 045.010, Ftime =279.740,Finteraction =20.130,P<0.001).α-SMA expression treated with sorafenib became weaker than that in control group(H=35.630,P<0.001).PDGF-BB and TGF-β1 concentrations decreased with the increasing of sorafenib concen-tration and time exposured(P<0.05).ERK1, ERK2 and AKT expression was identical between experimental and control groups, but their phosphorylated expression decreased with increased concentrations of sorafenib , especially in 10 μmol/L sorafenib group .Conclusion:Sorafenib could suppress HSC proliferation and activation .