中药新药与临床药理2025，Vol.36Issue(4)：552-563,12.DOI:10.19378/j.issn.1003-9783.2025.04.008
荣筋拈痛方调控滑膜巨噬细胞极化治疗膝骨关节炎性滑膜炎的网络药理学分析及验证
Network Pharmacology-Based Analysis and Experimental Verification of Rongjin Niantong Fang Regulating Synovial Macrophages Polarization in the Treatment of Knee Osteoarthritis Synovitis
摘要
Abstract
Objective To predict the effective components,potential targets and core signaling pathways of Rongjin Niantong Fang(RJNTF)in regulating macrophage M1 polarization in the treatment of knee osteoarthritis synovitis by network pharmacology analysis,then verified by in vitro and in vivo experiments.Methods The functional components of RJNTF were screened from the TCMSP database,and then the databases STITCH,Open Targets Platform and DrugBank were searched.The potential targets and signaling pathways of Rongjin Niantong Fang in regulating synovial macrophage polarization in the treatment of knee osteoarthritis were screened by gene chip analysis.Immunofluorescence,Western Blot and ELISA were used for verification.Results There are 36 potential targets of RJNTF in regulating macrophage polarization for the treatment of knee osteoarthritis.PPI network and gene enrichment analysis showed that RJNTF may regulate the polarization of macrophages by inhibiting NF-κB signaling pathway,thus playing a therapeutic role in knee osteoarthritis synovitis.In the animal experiment,HE results showed that compared with the blank group,the synovial membrane of the model group was significantly thicker than that of the blank group,the infiltration of synovial cells was increased,and the proliferation of pannus was significant.Compared with the model group,both the treatment group and the control group had thinner synovial thickness,less infiltrating cells on the inner surface of the synovial membrane and less proliferative pannus.ELISA results showed that compared with the blank group,the content of TNF-α in the synovial tissue of the model group was significantly increased(P<0.01).Compared with the model group,the content of TNF-α in the treatment group was significantly decreased(P<0.01).Western Blot results showed that compared with the blank group,p-NF-κB p65 was significantly activated in the model group(P<0.01),and the expression of p-NF-κB p65 was significantly inhibited in the treatment group(P<0.05).In vitro experiments,immunofluorescence results showed that compared with the blank group,the protein expressions of p-NF-κB p65 and CD16/32 in the model group were significantly enhanced.Compared with the model group,the protein expressions of p-NF-κB p65 and CD16/32 in the treatment group and the inhibitor group was significantly decreased.Western Blot results showed that compared with the blank group,the protein expression of TNF-α in the model group increased(P<0.01).Compared with the model group,the treatment group and the inhibitor group could reduce the protein expression of TNF-α in M1 macrophages(P<0.05,P<0.01).Compared with the blank group,the model group could significantly activate the phosphorylation of NF-κB p65 in macrophages(P<0.01).There was no significant effect on the total protein expression of NF-κB p65 in the treatment group and the inhibitor group,but compared with the model group,the treatment group(P<0.05)and the inhibitor group(P<0.01)could significantly reduce the phosphorylation of macrophage NF-κB p65.Conclusion RJNTF may regulate synovial macrophage polarization through NF-κB signaling pathway to treat knee osteoarthritis synovitis.关键词
膝骨关节炎/滑膜炎/巨噬细胞极化/网络药理学/荣筋拈痛方/R语言/实验验证/小鼠Key words
knee osteoarthritis/synovitis/macrophage polarization/network pharmacology/Rongjin Niantong Fang/R language/experimental verification/mice分类
医药卫生引用本文复制引用
王如意,张婷,李璐,陈楠,郑若曦,陈俊,吴广文..荣筋拈痛方调控滑膜巨噬细胞极化治疗膝骨关节炎性滑膜炎的网络药理学分析及验证[J].中药新药与临床药理,2025,36(4):552-563,12.基金项目
国家自然科学基金项目(82474553) （82474553）
福建省自然科学基金面上项目(2022J01843) （2022J01843）
国家中医药管理局高水平中医药重点学科建设项目(中医骨伤科学)(zyyzdxk-2023106) （中医骨伤科学）
福建中医药大学中医骨伤科学学科开放课题资助(XGS2023004) （XGS2023004）
福建省中青年教师教育科研项目(JAT210138). （JAT210138）
