中文摘要：

目的研究蛋白激酶C结合蛋白1（PICK1）在小鼠肝纤维及活化的肝星状细胞中的表达变化,并探讨其对人肝星状细胞株（LX-2）活化的影响。方法建立四氯化碳（CCl4）诱导的小鼠肝纤维化模型,观察PICK1在肝纤维化过程中的表达变化;转化生长因子β1（TGF-β1）刺激LX-2活化,Western blot测定PICK1的蛋白表达情况;转染PICK1过表达质粒至LX-2中,再以TGF-β1诱导活化,Western blot检测PICK1、α平滑肌肌动蛋白（α-SMA）、I型胶原（Col1a1）和Smad2、3及其磷酸化水平的蛋白表达情况。结果正常组小鼠肝脏中PICK1表达较高,随着肝纤维化的加重,PICK1的表达逐渐递减。TGF-β1诱导活化的LX-2细胞中PICK1表达降低。转染PICK1过表达质粒后,TGF-β1诱导的α-SMA、Colla1的表达明显减少,且Smad2、3磷酸化水平显著下降。结论 PICK1在纤维化肝组织及活化的HSC中表达下调。过表达PICK1可抑制TGF-β1诱导的LX-2活化,可能是通过抑制TGF-β/Smad通路而发挥作用,为肝纤维化的防治研究提供了新的思路和靶点。

英文摘要：

Objective To explore the expression of protein interacting with Ca-kinase-1（ PICK1） in fibrotic liver of mice and activated hepatic stellate cell,and investigate the effect of PICK1 on the activation of hepatic stellate cell strain（ LX-2）. Methods Liver fibrosis model in mice was induced by CCl4 and then the PICK1 level was detected in fibrotic liver tissue. LX-2 cells were activated by transforming growth factor β1（ TGF-β1）,and the protein level of PICK1 was detected by Western blot. After transfected with the plasmid expressing PICK1,LX-2 was stimulated with TGF-β1,the levels of α-smooth muscle actin（ α-SMA）,collagen type I（ Col1a1）,Smad2,3 and phosphorylation level of them were determined by Western blot. Results PICK1 was highly expressed in normal liver tissues and progressively down-regulated as liver fibrosis progressed. The expression of PICK1 was down-regulated in activated LX-2 induced by TGF-β1. The hepatic stellate cell transfected with PICK1-plasmid showed remarkablely decreased TGF-β1-induced α-SMA and Col1a1 expression and obviously declined phosphorylation levels of Smad2 and Smad3. Conclusion The expression of PICK1 decreases in fibrotic livers and activated hepatic stellate cell. Over-expression of PICK1 can suppress the activation of hepatic stellate cell induced by TGF-β1,and probably because of the inhibitory effect on TGF-β / Smad pathway,which provides new ideas and targets for the prevention and treatment of liver fibrosis.