褪黑素抑制内质网应激缓解对乙酰氨基酚诱导的急性肝损伤OA

Aim To investigate the protective effects of melatonin on acetaminophen(APAP)-induced acute liver injury and the underlying mechanisms.Methods An acute liver injury model was estab-lished in mice using APAP(350 mg·kg-1),followed by treatment with different doses of melatonin(25,50,100 mg·kg-1).In vitro,an endoplasmic reticulum stress(ERS)-induced model was induced in AML-12 hepatocytes using thiamphenicol(TM),treated with different concentrations of melatonin or 4-phenylbutyr-ate(4-PBA).Liver injury was assessed via HE stain-ing and serum ALT/AST levels.ERS-related mol-ecules were detected by Western blot and qPCR.Apoptosis was evaluated using Western blot,flow cy-tometry,and TUNEL staining.Results APAP-treated mice exhibited marked liver injury with signifi-cantly elevated serum ALT/AST levels and upregula-tion of ERS-related marker molecules(PERK,IRE1α,ATF6,etc.)at both protein and gene expres-sion levels.Melatonin dose-dependently ameliorated hepatocyte injury and reduced serum ALT/AST levels,with the 100 mg·kg-1 group showing the most pro-nounced effect.Additionally,melatonin significantly inhibited APAP-induced ERS markers and oxidative stress levels(decreased MDA levels and increased GSH levels),and reduced hepatocyte apoptosis.Nota-bly,4-PBA-mediated inhibition of endoplasmic reticu-lum stress also decreased APAP-induced apoptosis.Conclusion Melatonin alleviates APAP-induced acute liver injury by inhibiting endoplasmic reticulum stress and reducing hepatocyte apoptosis.