B细胞转录激活因子在非酒精性脂肪性肝炎中的表达及意义

Expression and significance of BATF in nonalcoholic steatohepatitis

目的通过构建蛋氨酸-胆碱缺乏(MCD)饮食诱导非酒精性脂肪性肝炎(NASH)小鼠模型,研究B细胞转录激活因子(BATF)在肝脏中表达水平,并探讨其与NASH进展的关系。方法C57BL/6小鼠共14只,随机分为对照组7只,MCD组7只。对照组正常饮食,MCD组给予MCD饮食8周建立NASH模型,通过实时荧光定量PCR、免疫组化、流式细胞术检测肝脏巨噬细胞中BATF表达情况,探讨BATF表达水平与临床指标的关系。结果与对照组相比,MCD组肝脏BATF和促炎因子TNF-α和IL-1βmRNA表达水平明显上调,且MCD组的BATF集中表达于间质炎细胞的细胞核。MCD组小鼠F4/80+标记库普弗细胞比例显著高于对照组,其中以CD11c+标记M1型库普弗细胞为主。BATF表达水平与肝脏生化ALT、AST以及肝脏组织学NAS评分、脂肪变、小叶炎症、气球样变均呈显著正相关。结论BATF参与NASH进展,在预测NASH进展中可能具有潜在价值。

Objective To investigate the expression of BATF in liver and explore its relationship with nonalcoholic steatohepatitis (NASH) progression by using NASH mouse model induced by a methionine-choline-deficient (MCD) diet. Methods C57BL/6 mice were given MCD diets for 8 weeks to establish NASH models.The expression of BATF in liver macrophage was detected by quantitative real-time polymerase chain reaction,immunohistochemistry and flow cytometry. Results Compared with non-specific control (NC) group,the messenger ribonucleic acid expression level of BATF and proinflammatory cytokines,such as tumor necrosis factor-α and interleukin-1β in MCD group,were significantly up-regulated.Besides,BATF was mainly expressed in the nuclei of inflammatory interstitial cells in MCD group.The proportion of F4/80-positive Kupffer cells in MCD group was significantly higher than that in NC group,which was mainly cluster of differentiation 11c-positive M1 Kupffer cells.BATF expression was significantly positively correlated with levels of alanine aminotransferase and aspartate aminotransferase,steatosis,lobular inflammation,ballooning and nonalcoholic fatty liver disease active score. Conclusion BATF is involved in the progression of NASH and might has a potential value in predicting the progress of NASH.