雷公藤甲素通过激活JNK通路诱发肝细胞损伤的机制研究OA

AIM:To investigate the role and mech-anism of triptolide(TP)in mediating liver cell dam-age through activation of the JNK pathway.METH-ODS:Using human hepatocellular carcinoma cells HepG2 and primary mouse hepatocytes,exposure to different doses(25,50,100 nmol/L)and times was conducted to assess liver cell viability and func-tion by measuring ALT and AST levels;Western blot-ting was employed to detect the expression levels of JNK pathway-related proteins;the JC-1 fluores-cent probe was used to detect changes in mito-chondrial membrane potential;the specific JNK in-hibitor SP600125(SP)was used for intervention ver-ification.RESULTS:After exposure to different dos-es of TP for 24 hours,the levels of ALT and AST in the culture medium significantly increased(P<0.05),simultaneously dose-dependently inhibiting HepG2 cell viability;Western blotting detected that p-JNK expression in HepG2 cells and mouse primary liver cells under different doses and times of TP treat-ment showed a positive correlation with TP concen-tration and exposure time;the JC-1 assay revealed significant changes in mitochondrial membrane po-tential in HepG2 cells treated with different doses of triptolide for 24 hours,leading to mitochondrial damage and inhibition of liver cell viability,with the degree of damage correlating positively with dose;pre-exposure to the JNK inhibitor SP significantly re-versed the TP-induced activation of p-JNK,resulting in significantly lower ALT and AST levels compared to the TP group(P<0.05),restoring cell viability.CONCLUSION:TP can significantly inhibit liver cell viability and impair their function,possibly by acti-vating the JNK pathway and causing mitochondrial damage.