肖剑伟 蔡旭 郭粉莲 黄新民 尹志华 汪荣盛

〔摘要〕 目的 通過网络药理学及分子对接、分子动力学探讨秦艽-桑枝治疗类风湿关节炎（RA）的活性成分、作用靶点及作用机制。方法 通过中药系统药理学技术平台（TCMSP）检索秦艽、桑枝的成分及作用靶点基因;将药对的作用靶点与GeneCards数据库检索所得的疾病靶基因取交集;根据交集结果进行GO功能富集和KEGG通路分析;通过Cytoscape得出核心基因;并选择PTGS2、CASP3、RELA等靶基因与秦艽、桑枝的活性成分山奈酚、β-谷甾醇、龙胆苦苷运用AutoDock Vina进行分子对接;通过Gromacs软件进行分子动力学模拟。结果 共筛选出秦艽-桑枝与RA共同靶基因90个。GO功能富集分析主要集中于对肿瘤坏死因子的反应、细胞调亡的调节、类固醇激素受体活性、肿瘤坏死因子受体超家族结合等。KEGG分析显示主要富集于TNF信号通路、调亡通路、IL-17信号通路、破骨细胞分化、类风湿关节炎等信号通路。分子对接及分子动力学结果显示药对的活性成分山奈酚、β-谷甾醇、龙胆苦苷能够与PTGS2、CASP3、RELA等靶基因紧密对接，形成稳定作用。结论 秦艽、桑枝的有效成分山奈酚、β-谷甾醇、龙胆苦苷可能通过作用于PTGS2、CASP3等靶基因，影响炎症因子释放及RA滑膜成纤维细胞的凋亡而发挥治疗RA的作用。

〔关键词〕 类风湿关节炎;分子对接;秦艽;桑枝;分子动力学;信号通路

〔中图分类号〕R255.6       〔文献标志码〕A       〔文章编号〕doi：10.3969/j.issn.1674-070X.2021.06.008

Mechanisms for the Treatment of Rheumatoid Arthritis with Qinjiao （Gentianae Macrophyllae Radix）-Sangzhi （Mori Ramulus） Based on Network Pharmacology， Molecular Docking

and Molecular Dynamics

XIAO Jianwei1， CAI Xu1， GUO Fenlian1， HUANG Xinmin1， YIN Zhihua1， WANG Rongsheng2*

（1. Shenzhen Futian Hospital for Rheumatic Diseases， Shenzhen， Guangdong 518000， China;

2. Shanghai Guanghua Hospital of Integrated Traditional and Western Medicin， Shanghai 200052， China）

〔Abstract〕 Objective To investigate the ingredients， target and mechanism of rheumatoid arthritis （RA） treated with Qinjiao （Gentianae Macrophyllae Radix）-Sangzhi （Mori Ramulus） by network pharmacology， molecular docking and molecular dynamics. Methods The ingredients and target genes of Qinjiao （Gentianae Macrophyllae Radix） and Sangzhi （Mori Ramulus） were searched through the Chinese medicine system pharmacology technology platform （TCMSP） and PharmMapper website， the intersection of the target of the drug pair and the disease target gene retrieved from the GeneCards database was taken， then gene ontology （GO） enrichment and KEGG pathway analysis based on the intersection results were performed. The Hub gene was obtained through Cytoscape. PTGS2， CASP3 and RELA with the active ingredients of Qinjiao （Gentianae Macrophyllae Radix）-Sangzhi （Mori Ramulus） including kaempferol， β-sitosterol and gentiopicroside were selected for molecular docking by AutoDock Vina. Molecular dynamics simulation was carried out by Gromacs software.  Results A total of 90 crossed target genes of Qinjiao （Gentianae Macrophyllae Radix）-Sangzhi （Mori Ramulus） and RA were identified. GO functional enrichment analysis mainly focused on the response to tumor necrosis factor， regulation of cell death， steroid hormone receptor activity， tumor necrosis factor receptor superfamily binding， etc. KEGG analysis showed that it was mainly enriched in TNF signaling pathway， apoptosis， IL-17 signaling pathway， osteoclast differentiation， rheumatoid arthritis， etc. The results of molecular docking and molecular dynamics showed that the active ingredients kaempferol， β-sitosterol and gentiopicroside of the drug pair can be closely docked with PTGS2， CASP3 and RELA， and to form a stable effect. Conclusion The effective ingredients kaempferol， β-sitosterol and gentiopicroside of Qinjiao （Gentianae Macrophyllae Radix）-Sangzhi （Mori Ramulus） may play a therapeutic role to affect the release of inflammatory factors and apoptosis of RA synovial fibroblasts by acting on the target genes such as PTGS2 and CASP3.

〔Keywords〕 rheumatoid arthritis; molecular docking; AutoDock Vina; Qinjiao-Sangzhi; R software; molecular dynamics

类风湿关节炎（rheumatoid arthritis， RA）是一种以慢性炎症和骨损伤为特征的自身炎症性疾病，其患病率约为0.5%～1%，其中，女性的发病率是男性的2～3倍[1]。其反复的滑膜炎症，最终导致关节软骨和骨损伤，从而出现功能限制、工作障碍和生活质量低下。……