时珍国医国药2025,Vol.36Issue(17):3228-3233,6.DOI:10.70976/j.1008-0805.SZGYGY-2025-1705
基于NLRP3/Caspase-1探讨大柴胡汤调节梗阻性胆汁淤积性肝损伤细胞焦亡的作用机制
Exploring the action mechanism of Dachaihu Decoction(大柴胡汤)in regulating pyroptosis in obstructive cholestatic liver injury based on the NLRP3/Caspase-1 pathway
摘要
Abstract
Objective To explore the action mechanism of Dachaihu Decoction(大柴胡汤,DCHD)in regulating hepatocyte pyroptosis through NLRP3/Caspase-1 pathway.Methods Forty eight SD rats were divided into the blank group,model group,high/medium/low-dose treatment groups,and positive control group,with 8 rats in each group.Three days after the modeling operation,the levels of ALP,GGT and DBIL were measured.After successful modeling,all treatment groups were respectively gavaged with different concentra-tions of DCHD granules,while the positive control group was given Ademetionine suspension.After one week,the levels of serum ALP and GGT were measured.The contents of serum IL-6,IL-1β,and IL-18 were detected by ELISA.The protein expressions of NL-RP3 and Caspase-1 in the liver tissues were detected by Western blot(WB).Results Compared with the blank group,all serological indicators in the model group were increased to varying degrees(P<0.01),and the protein levels of NLRP3 and Caspase-1 were in-creased(P<0.01).Compared with the model group,high/medium-dose treatment groups and the positive control group showed de-creased levels of ALP and GGT(P<0.01),while low-dose treatment group exhibited reduced levels of ALP(P<0.01)and GGT(P<0.05).All treatment groups and positive control group demonstrated decreased IL-6,IL-1 β,and IL-18 levels(P<0.05),with reduced protein expression levels of NLRP3 and Caspase-1(P<0.05).When comparing among the groups,high-dose group showed lower indices than the positive control group(P<0.01)and medium/low-dose treatment groups(P<0.05).Conclusion Hepatocyte pyroptosis is one of the pathogenesis mechanisms of obstructive cholestatic liver injury.DCHD can alleviate liver injury by effectively in-hibiting secretion of inflammatory factors of IL-6,IL-1β,and IL-18,inhibiting NLRP3/Caspase-1 and regulating hepatocyte py-roptosis.关键词
梗阻性胆汁淤积性肝损伤/大柴胡汤/核苷酸结合寡聚化结构域样受体3/半胱氨酸蛋白酶-1/细胞焦亡Key words
Obstructive cholestasis liver injury/Dachaihu Decoction(大柴胡汤)/NLRP3/Caspase-1/Pyroptosis分类
医药卫生引用本文复制引用
孟宪萌,陈维,关乐..基于NLRP3/Caspase-1探讨大柴胡汤调节梗阻性胆汁淤积性肝损伤细胞焦亡的作用机制[J].时珍国医国药,2025,36(17):3228-3233,6.基金项目
国家自然科学基金青年基金(82305222) (82305222)
沈阳市科技局公共卫生研发专项(中医药技术创新联合项目)(22-321-34-08) (中医药技术创新联合项目)
辽宁省自然科学基金计划项目(博士科研启动项目)(2024-BS-138) (博士科研启动项目)
辽宁省教育厅面上项目(LJKMZ20221339) (LJKMZ20221339)