摘要
目的探讨解耦联蛋白2(UCP2)在肝纤维化形成过程中的作用及其发生机制。方法体内实验采用四氯化碳(CCl4)诱导肝纤维化模型,取肝脏观察病理变化,用Western blotting、免疫组织化学和Real-time PCR等方法检测UCP2和p38丝裂素活化蛋白激酶(p38MAPK)的表达水平;体外实验采用UCP2特异性抑制剂京尼平和CCl4刺激星形细胞,检测UCP2和p38MAPK相关蛋白的表达情况。结果与正常组相比,模型组大鼠肝脏α-平滑肌肌动蛋白(α-SMA)和UCP2表达增高(P<0.05,n=10);加入CCl4刺激细胞后,星形细胞α-SMA表达增加,p38MAPK及其磷酸化水平增高(P<0.05,n=6);而在加入京尼平后,α-SMA表达增加,p38 MAPK及其磷酸化水平明显降低(P<0.05,n=6)。结论 UCP2参与了肝纤维化的发生,可能促进了星形细胞的活化及增殖过程。
Objective To explore the role of uncoupling protein 2 （ UCP2） in the development of hepatic fibrosis and its molecular mechanism .Methods The CCl4-induced liver fibrosis rat model in vivo was established to observe the pathological changes of rat livers .The expression levels of UCP2 and p38 mitogen activated protein kinase （p38 MAPK） were detected by using the techniques of Western blotting , Real-time PCR and immunohistochemistry .The hepatic stellate cells （ HSC） were stimulated by CCl 4 and UCP2-specific inhibitor Genipin to mimic liver fibrosis in vitro.The expression levels of UCP2 and p38MAPK were determined by using Western blotting .Results We found that UCP2 and α-SMA expression levels increased significantly （P ＆lt;0.05, n =10） in the liver of rats with CCl4-induced liver fibrosis when compared with that of the normal control rats in vivo.Similarly, the expression levels of UCP2 and p38 MAPK were up regulated （P ＆lt;0.05, n=6） in CCl4-treated HSC cells in vitro.However, the expressions of UCP2 and p38 MAPK were down regulated （P ＆lt;0.05, n=6） in genipin-treated HSC cells in vitro.Conclusion UCP2 is involved in liver fibrosis, and probably contributed to the activation and proliferation of hepatic stellate cells .
出处
《解剖学报》
CAS
CSCD
北大核心
2014年第4期480-484,共5页
Acta Anatomica Sinica
基金
国家自然科学基金资助项目(81272757)
