海南医科大学学报2025，Vol.31Issue(18)：1390-1398,9.DOI:10.13210/j.cnki.jhmu.20250515.004
基于TLR4/TRAF6/NF-κB/iNOS通路介导的巨噬细胞M1型极化探讨人参皂苷Rd抑制炎症治疗非酒精性脂肪性肝炎的机制研究
Mechanism study of ginsenoside Rd in inhibiting inflammation and treating non-alcoholic steatohepatitis based on TLR4/TRAF6/NF-κB/iNOS pathway-mediated M1 macrophage polarization
摘要
Abstract
Objective:To elucidate the effects of ginsenoside Rd on the TLR4/TRAF6/NF-κB/iNOS pathway and M1 mac-rophage polarization,thereby clarifying its molecular mechanism in treating non-alcoholic steatohepatitis(NASH).Methods:Mu-rine monocytic macrophage leukemia cells RAW264.7 were randomly divided into the control group,model group,low-dose gin-senoside Rd group,high-dose ginsenoside Rd group,and inhibitor group.Except for the control group,the remaining groups were induced with lipopolysaccharide to establish the model,followed by intervention with the corresponding drugs.Enzyme-linked im-munosorbent assay was employed to determine the concentrations of pro-inflammatory factors(TNF-α,IL-6,and IL-1β).The percentage of M1 macrophages was measured by flow cytometry.The expression of related molecules in the TLR4/TRAF6/NF-κB/iNOS pathway,autophagy,and ROS/p38/Nrf2 pathway was detected by Western blot and biochemical methods.The changes in macrophage autophagy levels were observed by transmission electron microscopy.Results:Compared to the model group,the levels of inflammatory factors(TNF-α,IL-6,and IL-1β)and the proportion of M1 macrophages were significantly re-duced in the ginsenoside Rd groups.The expression of TLR4,TRAF6,iNOS and nuclear p65 proteins showed notable downreg-ulation,whereas the nuclear p65 protein expression was significantly upregulated,and the differences were statistically significant(P<0.01).Additionally,ginsenoside Rd significantly increased the activity of SOD and the content of GSH,reduced the content of MDA,upregulated the expression of Beclin1 protein and the ratio of LC3Ⅱ/LC3Ⅰ,and downregulated the expression of cyto-plasmic p62,Nrf2 proteins,and the ratio of p-p38/p38,with statistically significant differences compared to the model group(P<0.01).Conclusion:Ginsenoside Rd inhibits M1 macrophage polarization by suppressing the activation of the TLR4/TRAF6/NF-κB/iNOS pathway,thereby alleviating NASH-related inflammation.Furthermore,ginsenoside Rd promotes autophagy by in-hibiting the ROS/p38/Nrf2 axis,which enhances the anti-inflammatory effects by suppressing M1 macrophage polarization.关键词
人参皂苷Rd/非酒精性脂肪性肝炎/巨噬细胞极化/炎症反应Key words
Ginsenoside Rd/Non-alcoholic steatohepatitis/Macrophage polarization/Inflammatory response分类
医药卫生引用本文复制引用
路瑶,李婧,王炳予,袁星星..基于TLR4/TRAF6/NF-κB/iNOS通路介导的巨噬细胞M1型极化探讨人参皂苷Rd抑制炎症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(18):1390-1398,9.基金项目
This study was supported by 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）
