海南医科大学学报2025，Vol.31Issue(16)：1220-1228,9.DOI:10.13210/j.cnki.jhmu.20250515.003
基于Derlin-1/PERK/eIF2α/CHOP信号通路探讨人参皂苷Rd抑制内质网应激治疗非酒精性脂肪性肝炎的机制研究
Mechanism of ginsenoside Rd in inhibiting endoplasmic reticulum stress for the treatment of non-alcoholic steatohepatitis via the Derlin-1/PERK/eIF2α/CHOP signaling pathway
摘要
Abstract
Objective:To investigate the effects of ginsenoside Rd on the Derlin-1/PERK/eIF2α/CHOP signaling pathway in hepatocytes,thereby elucidating its molecular mechanism in regulating endoplasmic reticulum stress for the treatment of non-alcoholic steatohepatitis(NASH).Methods:The cytotoxicity of ginsenoside Rd was assessed using the CCK8 assay.Subse-quently,a NASH cell model was established by inducing HepG2 cells with free fatty acids,followed by intervention with ginsen-oside Rd and an endoplasmic reticulum inhibitor.The effects of ginsenoside Rd on triglyceride(TG)levels,liver function,oxida-tive stress,cytokines,and the expression of key molecules in the Derlin-1/PERK/eIF2α/CHOP signaling pathway were evaluat-ed using Oil Red O staining,biochemical assays,immunofluorescence,enzyme-linked immunosorbent assay(ELISA),Western blotting,and real-time quantitative PCR.Results:Compared to the model group,ginsenoside Rd significantly reduced TG con-tent and the levels of AST and ALT in HepG2 cells,increased GSH content and SOD activity,and decreased MDA content and ROS mean fluorescence intensity,with statistically significant differences(P<0.01).Additionally,ginsenoside Rd significantly in-hibited the levels of TNF-α,IL-1β,CCL2,and CXCL1 in HepG2 cells,downregulated the expression of ATF4 and CHOP pro-teins,and reduced the ratios of p-PERK/PERK and p-eIF2α/eIF2α,with statistically significant differences compared to the mod-el group(P<0.01).Moreover,ginsenoside Rd intervention significantly suppressed the expression of Derlin-1 protein and mRNA,with statistically significant differences compared to the model group(P<0.01).Conclusion:Ginsenoside Rd inhibits the activation of the PERK/eIF2α/CHOP signaling pathway,thereby suppressing endoplasmic reticulum stress and exerting therapeu-tic effects on NASH.关键词
人参皂苷Rd/Derlin-1/内质网应激/非酒精性脂肪性肝炎Key words
Ginsenoside Rd/Derlin-1/Endoplasmic reticulum stress/Non-alcoholic steatohepatitis分类
医药卫生引用本文复制引用
路瑶,李丽萍,王炳予,袁星星..基于Derlin-1/PERK/eIF2α/CHOP信号通路探讨人参皂苷Rd抑制内质网应激治疗非酒精性脂肪性肝炎的机制研究[J].海南医科大学学报,2025,31(16):1220-1228,9.基金项目
This study was supported by the Excellent Youth Project of Natural Science Foundation of Heilongjiang Province(YQ2022H015) 黑龙江省自然科学基金优秀青年项目(YQ2022H015) （YQ2022H015）
