中国药理学通报2026，Vol.42Issue(9)：1653-1659,7.DOI:10.12360/CPB202510031
异补骨脂素诱导肝细胞过度自噬的肝毒性机制
The hepatotoxicity mechanism of isopsoralen involves inducing autophagy in primary hepatocytes from mice
摘要
Abstract
Aim To explore the role and mechanism of isopsoralen-induced autophagy in the hepatocyte damage it causes.Methods Hepatocytes were iso-lated from the livers of neonatal mice and their purity verified via immunofluorescence staining.Cell viabil-ity changes were assessed via the MTT assay;au-tophagy status was evaluated using the MDC assay and recombinant adenovirus transfection;the expressions of autophagy-and mitophagy-related proteins were ex-amined using Western blotting;cell viability was mea-sured before and after treatment with autophagy inhibi-tors 3-MA and BafA1,with subsequent observation of autophagy status and autophagy-related protein expres-sion.Results Hepatocytes were successfully isolated from the livers of ICR female mice with a purity of 0.858 7.Intraperitoneal(IP)administration exhib-ited toxic effects on primary hepatocytes,demonstrat-ing a dose-dependent response at 72 hours post-injection.Both the microcystin-D-cysteinyl-L-lysine(MDC)assay and recombinant adenovirus transfection methods indicated that IP induced autophagy in pri-mary hepatocytes,with autophagy rates increasing with higher doses.Western blot analysis of autophagy-related proteins revealed significantly elevated the ex-pression of Atg5,Beclin1,Pink1,and Parkin,along-side markedly reduced p62 expression.Inhibition with 3-MA and BafA1 reversed cellular autophagy,restored cell viability,and reverted the expression of auto phagy-associated proteins.Conclusions IP induces damage to primary mouse hepatocytes and can trigger hepatocyte autophagy.Inhibiting autophagy reduces IP's hepatocytic damage,suggesting that IP induces autophagy to precipitate liver injury.关键词
异补骨脂素/肝损伤/自噬/原代肝细胞/线粒体自噬/小鼠Key words
isopsoralen/liver injury/autophagy/pri-mary hepatocytes/mitochondrial autophagy/mice分类
医药卫生引用本文复制引用
周木子,王秀怡,孟昭君,李春丽,陈梦颖,王小莹,周昆..异补骨脂素诱导肝细胞过度自噬的肝毒性机制[J].中国药理学通报,2026,42(9):1653-1659,7.基金项目
国家重点研发计划(No 2022YFC3502103) （No 2022YFC3502103）
