中国实验方剂学杂志2026，Vol.32Issue(1)：39-46,8.DOI:10.13422/j.cnki.syfjx.20251195
茵陈蒿汤调控Fas/Caspase-8/Caspase-3信号通路改善胆汁淤积性肝损伤的机制
Mechanism Study of Yinchenhao Tang Regulating Fas/Caspase-8/Caspase-3 Signaling Pathway to Improve Cholestatic Liver Injury
摘要
Abstract
Objective:To explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6(Fas)/cysteine protease-8(Caspase-8)/cysteine protease-3(Caspase-3)signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury(CLI).Methods:Among 48 Wistar rats,12 rats were randomly selected as the blank group,and the other rats were administered alpha-naphthalene isothiocyanate(ANIT)by gavage to induce a CLI model.The modeling rats were randomly divided into the model group,the ursodeoxycholic acid group(0.1 g·kg-1)and the Yinchenhao Tang group(9.23 g·kg-1),with 12 rats in each group.The rats in each group were given corresponding drugs by gavage for three consecutive days.The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),gamma-glutamyl transpeptidase(γ-GT),total bilirubin(TBil)and total bile acid(TBA)in serum were detected.The levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in liver tissue were detected.The histopathological changes of the liver were observed by hematoxylin-eosin(HE)staining.The protein and mRNA expressions of Fas,Caspase-8,Caspase-3,B-cell lymphoma-2(Bcl-2)associated X protein(Bax)and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).Results:Compared with those in the blank group,the levels of ALT,AST,ALP,γ-GT,TBA and TBil in serum of the model group were significantly increased(P<0.01).The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased(P<0.01).The arrangement of hepatocytes was disordered,and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed.The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly increased(P<0.05,P<0.01),while the protein and mRNA expressions of Bcl-2 were significantly decreased(P<0.05,P<0.01).Compared with those in the model group,the levels of ALP,γ-GT,TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased.The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased(P<0.05,P<0.01).The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased(P<0.05,P<0.01),while the mRNA expression of Bcl-2 was significantly increased(P<0.05,).The levels of ALT,AST,γ-GT,TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased(P<0.01).The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased(P<0.05,P<0.01).The protein expression of Fas and Bax and the mRNA expression of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased(P<0.05,P<0.01),while the protein and mRNA expression of Bcl-2 were significantly increased(P<0.05,P<0.01).Hepatocyte injury,inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced.Conclusion:Yinchenhao Tang can ameliorate CLI,and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.关键词
茵陈蒿汤/胆汁淤积/肝损伤/肿瘤坏死因子受体超家族成员6(Fas)/胱天蛋白酶(Caspase)-8/Caspase-3通路Key words
Yinchenhao Tang/cholestasis/liver injury/tumor necrosis factor receptor superfamily member 6(Fas)/cysteinyl aspartate specific proteinase(Caspase)-8/Caspase-3 signaling pathway分类
医药卫生引用本文复制引用
ZHU Zhengwang,WANG Linlin,ZHAO Jinghan,SHE Linjing,TANG Yinpei,CAI Qingchun,WANG Bing,ZHU Pingsheng,MIAO Mingsan..茵陈蒿汤调控Fas/Caspase-8/Caspase-3信号通路改善胆汁淤积性肝损伤的机制[J].中国实验方剂学杂志,2026,32(1):39-46,8.基金项目
国家自然科学基金项目(82074340) （82074340）
河南省"双一流"创建学科中医学科学研究专项(HSRP-DFCTCM-2023-1-19,HSRP-DFCTCM-2023-8-32) （HSRP-DFCTCM-2023-1-19,HSRP-DFCTCM-2023-8-32）
河南省科技创新人才计划-杰出青年项目(154100510020) （154100510020）
