【摘要】 目的:观察法尼酯衍生物X受体(farnesoid X receptor,FXR)-促甲状腺素胚胎因子(thyrotropin embryonic factor,TEF)通路在自身免疫性肝炎模型小鼠肝损害中的作用,探讨FXR-TEF通路改善自身免疫性肝炎的部分可能机制。方法:检测FXR在伴刀豆球蛋白A(concanavalin A,Con A)诱导的肝炎(Con A-induced hepatitis,CIH)小鼠肝脏的表达;检测FXR激活对TEF表达的影响;观察C57BL/6小鼠和鹅去氧胆酸(chenodeoxycholic acid,CDCA)激活FXR的CIH小鼠肝脏病理、肝脏酶学及炎症因子变化。结果:FXR在CIH小鼠中低表达;CDCA激活FXR的C57BL/6小鼠TEF表达上调;FXR被激活的CIH小鼠的肝损害较轻,FXR激活可减轻肝脏炎症因子释放。结论:CDCA激活FXR能减轻CIH引起的肝功能损害和炎症反应。FXR激活使TEF上调。FXR可能是自身免疫性肝炎的保护因素,其保护作用可能是通过TEF来实现的。激活FXR可能成为治疗自身免疫性肝炎的一个途径。更多还原

【Abstract】 AIM: To observe how farnesoid X receptor( FXR) functioned in concanavalin A( Con A)-induced hepatitis( CIH) and the regulation of FXR-thyrotropin embryonic factor( TEF) pathway. METHODS: C57 BL /6 mice were injected with Con A to induce hepatitis. The expression of FXR and TEF in the liver specimens was determined by qRT-PCR and Western blotting. The concentrations of serum ALT /AST and inflammatory cytokines IFN-γ,TNF-α,IL-4 and IL-2 in the blood samples were tested after Con A injection. RESULTS: FXR was down-regulated in CIH mice. TEF was up-regulated when FXR was activated by chenodeoxycholic acid( CDCA). Activation of FXR reduced the levels of aminotransferases and inflammatory cytokines IFN-γ,TNF-α,IL-4 and IL-2 in the CIH mice induced by Con A injection. CONCLUSION:FXR activation attenuates CIH mouse liver injury and reduces inflammatory cytokines. FXR activation results in TEF up-regulation. The FXR-TEF pathway may play a protective role in autoimmune hepatitis.更多还原