活化的法尼醇X受体对自身免疫性肝炎细胞凋亡和肝损伤的影响  

Effect of activated farnesoid X receptor on apoptosis and liver damage in autoimmune hepatitis

作　　者：李政[1] 蒋晶晶[2] 朱月武[1] 李树华[1] 巫波[1] 苏明川 Li Zheng;Jiang Jingjing;Zhu Yuewu;Li Shuhua;Wu Bo;Su Mingchuan(Department of Clinical Laboratory,West China Fourth Hospital,Sichuan University,Chengdu 610041,China;Department of Clinical Laboratory,West China Hospital of Stomatology,Sichuan University y Chengdu 610041,China)

机构地区：[1]四川大学华西第四医院检验科,成都610041 [2]四川大学华西口腔医院检验科,成都610041

出　　处：《国际免疫学杂志》2019年第3期268-273,共6页International Journal of Immunology

摘　　要：目的分析法尼醇X受体(farnesoid X receptor,FXR)在自身免疫性肝炎(autoimmune hepatitis,AIH)中的保肝和抗细胞凋亡作用。方法选择60只雌性C57BL/6小鼠,随机分为四组:伴刀豆球蛋白A(concanavalin A,ConA)模型组、鹅去氧胆酸(chenodeoxycholic acid,CDCA)组、CDCA+ConA组和正常对照组,每组各15只。眼眶后静脉丛采集小鼠血液样品,检测氨基转移酶和炎性细胞因子的水平。收集小鼠肝脏标本,并使用HE染色进行组织病理学检查和检测。使用末端脱氧核苷酸-转移酶介导的dUTP缺口末端标记(terminal deoxynucleotidase-transferase-mediated dUTP nick end labeling,TUNEL)方法评估细胞凋亡情况。通过逆转录定量聚合酶链反应(reverse transcription-quantitative polymerase chain reaction,RT-qPCR)和Western blot方法分别测定凋亡相关基因和蛋白的表达水平。结果在ConA处理的小鼠中检测到转氨酶的活性增强。与正常组相比,炎性细胞因子干扰素-γ(interferon-γ,IFN-γ),肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),白细胞介素(interleukin,IL)-4和IL-2表达水平均增加(F分别为18.764,24.377,24.573和26.482,P值均<0.05)。用FXR激动剂CDCA预处理的小鼠对ConA肝炎的抗性更强,与ConA组相比,丙氨酸转氨酶/天冬氨酸氨基转移酶的表达水平显著降低(t=13.595,P<0.05)。FXR在ConA诱导的肝炎诱导的小鼠肝脏标本中的mRNA水平显著下调(t=6.846,P<0.05);CDCA组FXR的mRNA水平显著上升(t=17.841,P<0.05)。与ConA组相比,CDCA+ConA组在第4,8和12 h显著降低(t值分别为5.386、14.485、9.385,P值均<0.05)。结论FXR激活改善了肝损伤并抑制了ConA诱导的肝炎中的炎性细胞因子。因此,推测FXR对ConA诱导的细胞凋亡发挥保护作用。Objective To analyze the hepatoprotective and anti-apoptotic effects of farnesoid X receptor(FXR)in autoimmune hepatitis(AIH).Methods Total of 60 female C57BL/6 mice were divided into four groups randomly:the concanavalin A(ConA)model group,the chenodeoxycholic acid(CDCA)group,the CDCA+ConA group and the normal control group,with 15 mice in each group.Blood samples of mice collected from retro-orbital venous plexus and were obtained to detect levels of aminotransferase and inflammatory cytokines.The liver specimens were collected,and the histopathological examination and detection were performed by HE staining.The cell apoptosis was assessed by the terminal deoxynucleotidase-transferase-mediated dUTP nick end labeling(TUNEL)method.The expression levels of apoptosis-related genes and proteins were determined by reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blot respectively.Results The increase of transaminase activity and inflammatory cytokines levels were detected in ConA-treated mice.Compared with control group,the expression of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin(IL)-4 and IL-2 were increased in ConA-treated mice(F values were 18.764,24.377,24.573 and 26.482 respectively,all P values<0.05).The mice pretreated with the FXR agonist CDCA were more resistant to ConA hepatitis.Compared to the ConA group,the expression level of alanine aminotransferase/aspartate aminotransferase was significantly lower(t=13.595,P<0.05).The mRNA level of FXR in ConA-induced hepatitis-induced liver samples was significantly down-regulated(t=6.846,P<0.05).The mRNA level of FXR in the CDCA group was significantly increased(t=17.841,P<0.05).Compared with the ConA group,the mRNA level of FXR in the CDCA+ConA group was significantly lower at 4,8 and 12 h(t values were 5.386,14.485,9.385 respectively,all P values<0.05).Conclusion FXR activation improves liver injury and inhibits inflammatory cytokines in ConA-induced hepatitis.FXR may be exert a protective effect on ConA-indu

关 键 词：自身免疫性肝炎 伴刀豆球蛋白A诱导的肝炎 法尼醇X受体 细胞凋亡 

分 类 号：R575.1[医药卫生—消化系统]