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黄婷, 朱权, 陈纯静, 佘颜, 罗卉, 卢芳国.真武汤与芍药苷在系统性红斑狼疮中的作用及机制探讨[J].湖南中医药大学学报英文版,2025,45(3):453-459.[Click to copy
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真武汤与芍药苷在系统性红斑狼疮中的作用及机制探讨 |
黄婷,朱权,陈纯静,佘颜,罗卉,卢芳国 |
(湖南中医药大学, 湖南 长沙 410208;中南大学湘雅医院风湿免疫科, 湖南 长沙 410008) |
摘要: |
目的 基于网络药理学和实验研究探讨真武汤(ZWD)及其关键成分芍药苷(PF)在系统性红斑狼疮(SLE)中的治疗作用及机制。方法 利用TCMSP数据库获取ZWD关键成分PF对应的靶基因信息;通过GeneCards、OMIM数据库获取SLE疾病相关靶基因;通过韦恩图对PF靶基因与SLE疾病靶基因进行交集分析获取关键靶点,并利用STRING平台构建关键靶点的蛋白质-蛋白质相互作用网络模型;使用基因注释与分析平台DAVID 6.8对关键靶点进行GO功能富集分析和KEGG通路富集分析。体外实验验证:选用小鼠巨噬细胞样细胞系RAW 264.7,实验分为空白对照组,R848诱导组(使用R848 8 μg/mL诱导RAW 264.7细胞炎性极化48 h),PF治疗组(在R848诱导极化的第24小时予以80 μmol/L处理24 h),2.5%、5%ZWD治疗组(在R848诱导极化的第24小时予以2.5%、5%ZWD含药血清处理24 h)。采用流式细胞术检测CD86、CD206的表达情况,以明确M1型和M2型巨噬细胞比例,评估ZWD和PF对巨噬细胞炎性极化的影响。结果 网络药理学分析表明,PF有74个药物靶基因,其中26个为SLE中的关键致病基因。GO功能富集分析显示PF治疗SLE的靶基因主要作用于细胞趋化、增殖调节和酶结合过程。KEGG通路富集显示PF调控单核巨噬细胞的生物学功能及炎症反应相关通路,尤其是磷酸肌醇3-激酶蛋白(PI3K)/丝氨酸/苏氨酸蛋白激酶(Akt)通路、核转录因子(NF-κB)通路、丝裂原活化蛋白激酶(MAPK)通路和Janus激酶/信号转导与转录激活子(JAK/STAT)通路,且这些通路在SLE的发病机制中起着核心作用。体外细胞学实验显示,与空白对照组比较,R848诱导组CD86M1型巨噬细胞比例显著上升(P<0.001,P<0.000 1);与R848组比较,PF组、2.5%ZWD组、5%ZWD组CD86 M1型巨噬细胞比例均显著下降(P<0.001,P<0.000 1)。结论 中药复方ZWD及其关键活性成分PF可能通过抑制单核/巨噬细胞向M1表型极化,干预炎症反应,实现其在SLE治疗中的潜在效用。 |
关键词: 系统性红斑狼疮 真武汤 芍药苷 单核细胞 网络药理学 |
DOI:10.3969/j.issn.1674-070X.2025.03.009 |
Received:November 27, 2024 |
基金项目:国家自然科学基金项目(82074250);湖南省自然科学基金青年项目(2025JJ60529);湖南省教育厅优秀青年项目(24B0341)。 |
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Effects and mechanisms of Zhenwu Decoction and paeoniflorin in treating systemic lupus erythematosus |
HUANG Ting, ZHU Quan, CHEN Chunjing, SHE Yan, LUO Hui, LU Fangguo |
(Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Department of Rheumatology and Immunology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China) |
Abstract: |
Objective To elucidate the therapeutic effects and mechanisms of Zhenwu Decoction (ZWD) and its key component paeoniflorin (PF) in systemic lupus erythematosus (SLE) based on network pharmacology and experimental studies. Methods The target gene information corresponding to PF, the key component of ZWD, was obtained from the TCMSP database. SLE-related target genes were retrieved from the GeneCards and OMIM platforms. Key targets were identified through Venn diagram analysis of the intersection between PF target genes and SLE disease target genes. The STRING platform was used to construct a protein-protein interaction network model for the key targets. The gene annotation and analysis platform DAVID 6.8 was employed for GO functional enrichment analysis and KEGG pathway enrichment analysis of the key targets. In vitro experiments validation, mouse macrophage-like cell line RAW 264.7 was selected. The experiment included blank control group, R848-induced group (RAW 264.7 cells were induced to inflammatory polarization with 8 μg/mL R848 for 48 h), PF treatment group (treated with 80 μmol/L PF for 24 h starting from the 24th hour of R848 induction), and 2.5% and 5% ZWD treatment groups (treated with 2.5% and 5% ZWD medicated serum for 24 h starting from the 24th hour of R848 induction). Flow cytometry was used to check the CD86 and CD206 expressions to determine the proportion of M1 and M2 macrophages and assess the effects of ZWD and PF on macrophage inflammatory polarization. Results Network pharmacology analysis revealed that there were 74 drug target genes in PF, and 26 of which were key pathogenic genes for SLE. GO functional enrichment analysis showed that PF mainly acted on cell chemotaxis, proliferation regulation, and enzyme binding processes. KEGG pathway enrichment analysis indicated that PF can regulate biological functions of monocytes/macrophages and inflammation-related pathways, especially the phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt) pathway, nuclear transcription factor (NF-κB) pathway, mitogen-activated protein kinase (MAPK) pathway, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, which played core roles in the pathogenesis of SLE. In vitro cellular experiments showed that compared with the blank control group, the proportion of CD86 M1 macrophages in the R848-induced group significantly increased (P<0.001, P<0.000 1). Compared with the R848-induced group, the proportions of CD86 M1 macrophages in the PF group, 2.5% ZWD group, and 5% ZWD group all notably decreased (P<0.001, P<0.000 1). Conclusion Chinese medicine compound formula ZWD and its key active component PF may exert their potential utility in the treatment of SLE by inhibiting the polarization of monocytes/macrophages towards the M1 phenotype and intervening in the inflammatory response. |
Key words: systemic lupus erythematosus Zhenwu Decoction paeoniflorin monocytes network pharmacology |
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