南方医科大学学报2025，Vol.45Issue(4)：810-818,9.DOI:10.12122/j.issn.1673-4254.2025.04.16
梓醇扶正制毒配伍从SLC7A11/GPX4通路抑制铁死亡减轻雷公藤甲素肝毒性
Catalpol reduces liver toxicity of triptolide in mice by inhibiting hepatocyte ferroptosis through the SLC7A11/GPX4 pathway:testing the Fuzheng Zhidu theory for detoxification
摘要
Abstract
Objective To investigate the protective effect of catalpol against triptolide-induced liver injury and explore its mechanism to test the Fuzheng Zhidu theory for detoxification.Methods C57BL/6J mice were randomized into blank control group,catalpol group,triptolide group and triptolide+catalpol group.After 13 days of treatment with the agents by gavage,the mice were examined for liver tissue pathology,liver function,hepatocyte subcellular structure,lipid peroxidation,ferrous ion deposition and expressions of ferroptosis-related proteins in the liver.In a liver cell line HL7702,the effect of catalpol or the ferroptosis inhibitor Fer-1 on triptolide-induced cytotoxicity was tested by examining cell functions,Fe2+concentration,lipid peroxidation,ROS level and the ferroptosis-related proteins.Results In C57BL/6J mice,catalpol significantly alleviated triptolide-induced hepatic injury,lowered the levels of ALT,AST and LDH,and reversed the elevation of Fe2+concentration and MDA level and the reduction of GPX level.In HL7702 cells,inhibition of ferroptosis by Fer-1 significantly reversed triptolide-induced elevation of ALT,AST and LDH levels.Western blotting and qRT-PCR demonstrated that catalpol reversed abnormalities in expressions of SLC7A11,FTH1 and GPX4 at both the mRNA and protein levels in triptolide-treated HL7702 cells.Conclusion The combined use of catalpol can reduce the hepatotoxicity of triptolide in mice by inhibiting excessive hepatocyte ferroptosis through the SLC7A11/GPX4 pathway.关键词
梓醇/雷公藤甲素/肝毒性/铁死亡Key words
catalpol/triptolide/hepatotoxicity/ferroptosis引用本文复制引用
张林落,李长青,皇玲玲,周学平,娄媛媛..梓醇扶正制毒配伍从SLC7A11/GPX4通路抑制铁死亡减轻雷公藤甲素肝毒性[J].南方医科大学学报,2025,45(4):810-818,9.基金项目
中国中医科学院学部委员学术传承与传播专项项目(CL2022E028XB) （CL2022E028XB）
江苏省高校自然科学研究课题面上项目(23KJD330001) （23KJD330001）
江苏省中医药科技发展计划课题面上项目(MS2024136) （MS2024136）
淮安市基础研究计划自然科学研究课题面上项目(HAB2024076) （HAB2024076）
江苏高校"青蓝工程" （）
江苏护理职业学院科研创新研究团队项目(SHCXTD2023052904) （SHCXTD2023052904）
