中国药理学通报2025，Vol.41Issue(7)：1283-1289,7.DOI:10.12360/CPB202412070
苦参碱通过抑制CBS/H2S/ATP5A通路诱导肝毒性
Matrine induces hepatotoxicity by inhibiting CBS/H2S/ATP5A pathway
摘要
Abstract
Aim To elucidate the mechanism of ma-trine(MT)-induced liver damage.Methods After ex-posure of L02 cells and BALB/c mice to MT,mouse hepatic function,histopathological examinations of the liver,cell viability of L02 cells,reactive oxygen spe-cies(ROS)levels,mitochondrial function,apoptosis,and cystathionine β-synthase(CBS)/H2S/ATP syn-thase F1 subunit alpha(ATP5 A)pathway activity were detected.Results MT treatment decreased L02 cell viabilities in a dose-dependent manner.MT also decreased the levels of CBS and ATP5A S-sulfhydra-tion,increased ROS levels,depolarized the mitochon-drial membrane potential,decreased the biosynthesis of H2S and ATP,ultimately activated the caspase-3 activ-ity and apoptosis(P＜0.05).In vivo experiments showed that MT induced severe liver injury in BALB/c mice,along with a decline in CBS,SH-ATP5A,H2S,and ATP levels,and caspase-3 activation(P＜0.05).However,either NaHS treatment or methionine treat-ment reversed MT-induced apoptosis and hepatotoxicity by increasing the intracellular H2S levels in vivo and in vitro(P＜0.05).Conclusions MT induces ROS ac-cumulation,mitochondrial dysfunction,caspase-3 acti-vation and apoptosis by inhibiting the CBS/H2S/ATP5A pathway.The upregulation of intracellular H2S levels partially reverses MT-induced hepatotoxicity via ATP5A S-sulfhydration.关键词
苦参碱/CBS/H2S/ATP5A/凋亡/肝毒性Key words
matrine/CBS/H2S/ATP5A/apoptosis/hepatotoxicity分类
医药卫生引用本文复制引用
席晨,魏静瑶,周婕..苦参碱通过抑制CBS/H2S/ATP5A通路诱导肝毒性[J].中国药理学通报,2025,41(7):1283-1289,7.基金项目
国家自然科学基金资助项目(No 82460815) （No 82460815）
