CYP2E1在小鼠酒精性肝纤维化中的作用研究

The role of CYP2E1 in alcoholic liver fibrosis in mice

目的探讨CYP2E1在酒精性肝纤维化(ALF)过程中的作用。方法取健康雄性C57BL/6J小鼠随机分为2组:正常组(n=10)和实验组(n=40),正常组用Lieber-DeCarli液体饲料饲养小鼠8周,实验组用Lieber-DeCarli液体酒精饲料饲养,4周后联合5%CCl 4-橄榄油2 ml/kg进行腹腔注射,2次/周,进行ALF造模,共8周。分别于0、2、4、6、8周每组各取4只小鼠进行眼球采血以检测血清中ALT活性;颈椎脱臼处死小鼠取肝,HE染色观察肝组织病理学形态改变和坏死得分;蛋白免疫印迹法检测CYP2E1的表达水平。结果与正常组相比,实验组肝功能指标和肝纤维化水平逐渐升高,在造模第4周时出现最严重肝损伤(P<0.01)。随着造模时间的延长,肝脏出现不同程度的损伤修复现象,且CYP2E1表达量逐渐降低。结论CYP2E1的表达在ALF形成过程中起一定的作用。

Objective To investigate the role of CYP2E1 in the process of alcoholic liver fibrosis(ALF).Methods Fifty healthy male C57BL/6J mice were randomly divided into 2 groups:normal group(n=10)and experimental group(n=40).The normal mice were fed with Lieber-DeCarli liquid diet for 8 weeks.The experimental group was treated with Lieber-DeCarli liquid alcohol feed,after 4 weeks,combined with 5%CCl 4 olive oil 2 ml/kg for intraperitoneal injection,2 times a week,to model ALF for 8 weeks.4 mice were taken at 0,2,4,6 and 8 weeks respectively for eyeball sampling to detect ALT activity in serum;mice were sacrificed by cervical dislocation to take liver,and HE staining was used to observe the pathological changes and necrosis rate of liver tissue;Western blotting was used to detect the expression level of CYP2E1.Results Compared with the normal group of mice,the liver function indexes and liver fibrosis level of the experimental group gradually increased,and the most severe liver damage occurred at the 4th week of modeling(P<0.01).With the prolongation of the modeling time,the liver showed different degrees of damage and repair,and the expression of CYP2E1 gradually decreased.Conclusion The expression of CYP2E1 plays a certain role in the formation of ALF.