Nrf2对肝纤维化过程中炎症细胞的影响
Effects of nuclear factor-E2 related factor 2 on inflammatory cells during liver fibrosis

目的:探索在四氯化碳诱导小鼠肝纤维化形成过程中,核因子相关因子2(Nrf2)对炎症细胞浸润的影响。方法:野生鼠和Nrf2基因敲除鼠各24只,分别随机平均分成对照组和模型组。HE染色、Masson三色染色观察肝组织病理学变化及肝脏纤维化程度; 天狼星红染色观察胶原沉积情况; 免疫组化方法检测肝组织中中性粒细胞浸润(Ly6-G阳性)情况; 免疫荧光方法检测巨噬细胞浸润及活化(ER-MP23阳性)情况。结果:两个对照组均未有肝纤维化表现; 基因敲除模型组小鼠肝组织坏死及纤维化程度重于野生模型组,胶原含量更多(P<0.05)。四氯化碳诱导可增强肝组织中中性粒细胞的浸润,但基因敲除鼠中性粒细胞浸润轻于野生模型鼠(P<0.05)。Nrf2基因敲除和四氯化碳诱导均增强肝组织中巨噬细胞的活化,两者具有协同效应(P<0.05)。结论:Nrf2可以通过抑制巨噬细胞活化抑制四氯化碳诱导的肝纤维化发展。
Aim: To investigate the effects of nuclear factor-E2 related factor 2(Nrf2)on infiltration of inflammatory cells from rats with CCl4-induced liver fibrosis.Methods: There were four groups including wild type(WT)control group(WT mice without CCl4-induction), WT-CCl4 group(WT mice with CCl4-induction), Nrf2 knockout(Nrf2-/-)control group(Nrf2-/- mice without CCl4-induction)and Nrf2-/--CCl4 group(Nrf2-/- mice with CCl4-induction), and 12 in each group. Histological morphology was studied by HE staining,Masson triple staining, and Sirius red staining was used to observe the deposition of collagen.Neutrophils(labelled by Ly6-G )and macrophages(labelled by ER-MP23)infiltration were detected by immunohistochemical staining and immunofluorescence,respectively.Results: The two control groups had no liver fibrosis pathogenic manifestations; the liver fibrosis was more severe and collagen content was higher in Nrf2-/--CCl4 group than those in WT-CCl4 group(P<0.05).In the WT-CCl4 group,the infiltration of neutrophils were increased obviously compared with control groups,but there was a significant decrease in the Nrf2-/--CCl4 group when compared with the WT-CCl4 group(P<0.05).The macrophages were infiltrated and activated in the model groups than in the control groups,especially in the Nrf2-/--CCl4 group(P<0.05).Conclusion: Nrf2 plays a protective role in CCl4-induced liver fibrosis via inhibiting the activation of macrophages