成纤维细胞生长因子21在酒精性肝纤维化形成中的作用

Role of fibroblast growth factor 21 in pathogenesis of alcoholic liver fibrosis

目的探讨成纤维细胞生长因子-21(fibroblast growth factor21,FGF21)在酒精性肝纤维化形成中的作用。方法将80只雄性SD大鼠随机分为空白组(10只)、四氯化碳(CCl4)组(10只)和造模组(60只)。造模组采用每日酒精混合物灌胃及1周两次微量CCl4混合液腹腔注射,连续12周。分别于4、8、10、12周处死大鼠,观察大鼠肝组织病理学改变;采用免疫组化法、蛋白质印迹、荧光定量PCR检测FGF21蛋白和mRNA表达动态变化。结果与空白组比较,造模组肝纤维化程度明显加重;FGF21水平空白组为(0.23±0.01),造模组在第4周明显增加为(1.06±0.10),之后逐渐升高到第10周为(1.36±0.16),到12周时却明显下降为(1.08±0.11)。结论 FGF21在酒精性肝纤维化形成中具有重要作用,在肝损害过程中FGF21应激性升高,在FGF21分泌不足时出现明显的肝纤维化,增加FGF21可能是治疗酒精性肝纤维化的另一个靶点。

Objective To observe the dynamic variety of fibroblast growth factor 21（FGF21）in the development of alcoholic liver fibrosis in rats,and further investigate the role of FGF21 in alcoholic liver fibrosis.Methods Male SD rats weighing 240-280 g were randomly divided into blank group,carbon tetrachloride（CCl4）group and model group.The model was built with 10 mL/kg of alcohol mixture（56 DEG of alcohol：corn oil：pyrazole=5∶1∶10）by gavage daily and0.3 ml/kg CCl4 mixture（CCl4∶olive oil=1∶3）by intraperitoneal injection twice a week for 12 weeks.The rats were sacrificed at week 4,8,10 and 12,respectively.Pathological changes in liver tissue were observed.Immunohistochemistry,western blot and fluorescent quantitative polymerase chain reaction（PCR）were used to measure FGF21 expression.ResultsCompared with blank group,the severity of liver fibrosis in model group was significantly increased.Level of FGF21 was significantly increased at week 4（1.06±0.10 vs 0.23± 0.01,P〈0.05）,and then gradually increased till week 10（1.36±0.16 vs 1.06±0.10,P〈0.05）,while significantly decreased at week12 compared with that at week10（1.08±0.11 vs1.36±0.16,P〈0.05）.Conclusion FGF21 might play a key role in the development of alcoholic liver fibrosis.Level of FGF21 was elevated under stress during liver injury and decreased when fibrosis developed.Therefore,increasing the level of FGF21 might be a potential target for treatment of alcoholic liver fibrosis.