中国免疫学杂志2025，Vol.41Issue(11)：2624-2630,7.DOI:10.3969/j.issn.1000-484X.2025.11.012
丹参总酚酸调控TLR4/MyD88/NF-κB通路改善肝癌荷瘤小鼠髓源性巨噬细胞浸润的作用机制
Mechanism of total salvianolic acid improving myeloid macrophage infiltration in liver cancer bearing mice by regulating TLR4/MyD88/NF-κB pathway
摘要
Abstract
Objective:To investigate the impacts of total salvianolic acid(TSA)on macrophage polarization and mesenchymal macrophage infiltration in liver cancer bearing mice by regulating the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods:Mice were randomly separated into liver cancer group,TSA low concentra-tion group,TSA medium concentration group,TSA high concentration group,TSA high concentration+TLR4 inhibitor(TAK242)group and control group,with 12 mice in each group.Except for control group,mice in all other groups were injected subcutaneously into the right axilla to construct liver cancer models by intraperitoneal transmission of third-generation H22 cell suspension.After suc-cessful modeling,administration was carried out once a day for 2 weeks.Changes in tumor weight,tumor volume,spleen index and thymus index were detected.Immunofluorescence was applied to detect proportions of CD86 and CD206 positive cells in tumor tissue.ELISA was applied to detect levels of inducible nitric oxide synthase(iNOS),IL-6 and IL-10 in tumor tissues.Flow cytometry was ap-plied to detect proportion of CD11b+F4/80+in tumor tissue.Western blot was applied to detect TLR4,p-NF-κB P65 and MyD88 pro-teins in tumor tissue.The life quality and survival rate of mice were observed.Results:Compared with control group,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were reduced in liver cancer group,while proportion of CD206 positive cells and level of IL-10 in tumor tissue were increased(P<0.05).Compared with liver cancer group,tumor weight and volume of mice in TSA low,medium,high concentration groups were decreased,while survival rate,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were increased,proportion of CD206 positive cells,level of IL-10,and proportion of CD11b+F4/80+in tumor tissue decreased(P<0.05).TAK242 reversed the effects of high concentration TSA on macrophage polarization and myeloid macrophage infiltration in liver cancer bearing mice.Conclusion:TSA may promote M1 polari-zation of macrophages in liver cancer bearing mice and inhibit myeloid macrophage infiltration by activating the TLR4/MyD88/NF-κB pathway.关键词
丹参总酚酸/肝癌/巨噬细胞极化/髓源性巨噬细胞浸润Key words
Total salvianolic acid/Liver cancer/Macrophage polarization/Mesenchymal macrophage infiltration分类
中医学引用本文复制引用
杜雨楠,党志博,张希倩,谭高峰,李洪霖,贾云飞..丹参总酚酸调控TLR4/MyD88/NF-κB通路改善肝癌荷瘤小鼠髓源性巨噬细胞浸润的作用机制[J].中国免疫学杂志,2025,41(11):2624-2630,7.基金项目
河南省中医药科学研究专项课题(2023ZY2062). （2023ZY2062）
