降酶退黄合剂治疗急性肝损伤的作用机制研究OACHSSCD

Objective:To investigate the protective effects and mechanisms of Jiangmei Tuihuang Mixture(JTM)on hepatocytes in an acute liver injury model based on the miRNA-103/phosphatase and tensin homolog(PTEN)/endoplasmic reticulum stress(ERS)signaling pathway.Methods:Human hepatocyte cell line HHL-5 was routinely cultured and divided into a blank group,a model group,a JTM group,a miR-103-3p inhibitor negative control(NC)group,a miR-103-3p inhibitor group,and a miR-103-3p inhibitor+JTM group.JTM-containing serum was prepared.The CCK-8 assay was used to determine the optimal drug concentration and exposure time for intervention.Western blot(WB)and quantitative reverse transcription-polymerase chain reaction(qRT-PCR)were used to detect the mRNA and protein expression levels of miR-103-3p and PTEN/ERS pathway-related molecules in HHL-5 cells.Results:Compared with the blank group,the model group showed significantly increased mRNA and protein expression levels of miR-103-3p and PTEN/ERS pathway-related molecules(P＜0.05).Compared with the model group,the JTM group and the miR-103-3p inhibitor+JTM group showed decreased mRNA expression levels of miR-103-3p,PTEN,glucose-regulated protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),activating transcription factor 4(ATF4),C/EBP homolo-gous protein(CHOP),activating transcription factor 6(ATF6),phosphorylated inositol-requiring enzyme 1(p-IREl),and X-box binding protein 1(XBP-1),with the most significant effect observed in the miR-103-3p inhibitor+JTM group(P＜0.01).Protein expression levels of PTEN,GRP78,PERK,ATF4,CHOP,ATF6,p-IREl,and XBP-1 were also decreased,with the miR-103-3p in-hibitor+JTM group showing a more significant effect(P＜0.05).Conclusion:JTM can exert hepatoprotective effects by downregu-lating miR-103-3p expression in hepatocytes with acute liver injury,thereby blocking PTEN/ERS signal transduction,preventing endoplasmic reticulum dysfunction,and ultimately protecting liver function.