基于网络药理学探讨驱风止痛散治疗急性痛风性关节炎的作用及其机制  

Exploring the effects and mechanisms of Qufeng Zhitong San in the treatment of acute gouty arthritis based on network pharmacology

作　　者：郭思彤[1] 谭思涛 梁小玲 黄菊 刘丽敏[2] Guo Sitong;Tan Sitao;Liang Xiaoling;Huang Ju;Liu Limin(Department of Pharmacy,People’s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,China;School of Pharmacy,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西壮族自治区人民医院药学部,南宁530021 [2]广西医科大学药学院,南宁530021

出　　处：《广西医科大学学报》2022年第3期431-436,共6页Journal of Guangxi Medical University

基　　金：广西高校科学技术研究基金资助项目(No.KY2015YB059);广西卫生健康委自筹经费科研基金资助项目(No.Z20210684)。

摘　　要：目的:研究驱风止痛散(QFZTS)治疗急性痛风性关节炎(AGA)的疗效及作用机制。方法:在TCMSP平台和Pubchem数据库筛选QFZTS活性成分及作用靶点,Genecards、OMIM数据库获取疾病靶点,将药物与疾病相关靶点取交集生成韦恩图,即得到QFZTS治疗AGA的潜在靶点。运用STRING数据库构建PPI网络图,导入CytoScape3.7.1得到潜在的关键靶点基因,进而对关键靶点基因进行KEGG通路分析。将60只SD大鼠随机分为空白组、模型组、秋水仙碱组和QFZTS高、中、低剂量组,除空白组外,其他各组通过踝关节腔内注射尿酸钠(MSU)混悬液复制AGA模型。采用苏木精—伊红(HE)染色观察踝关节滑膜组织病理学变化,酶联免疫吸附试验(ELISA)法检测血清白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α和转化生长因子(TGF)-β1水平,RT-qPCR法检测踝关节周围软组织中炎性小体NLRP3、Caspase-1、IL-1βm RNA表达。结果:QFZTS与AGA相关度最高的前20个靶点有MAPK14、CXCL8、CRP、IL-1β、NLRP3、CASP1、IL-6、TNF及TGF-β1等,其中炎症因子发挥重要作用。与模型组比较,QFZTS高剂量组大鼠血清中IL-1β、IL-6、TNF-α、TGF-β1水平降低,QFZTS高、中剂量组踝关节周围软组织中NLRP3、Caspase-1、IL-1βmRNA表达下调(P<0.05),滑膜增生情况均有不同程度的改善,炎性细胞浸润减少。结论:QFZTS可能通过下调NOD样受体信号通路相关炎症因子抑制AGA。Objective:To study the effects and mechanisms of Qufeng Zhitong San (QFZTS) in the treatment of acute gouty arthritis (AGA).Methods:The active ingredients and action targets of QFZTS were screened in TC-MSP platform and Pubchem database,and the disease targets were obtained from Genecards and OMIM databases.The intersection of the drug and the disease- related targets were taken to generate a Venn diagram,which yielded the potential targets of QFZTS for the treatment of AGA.The STRING database was used to construct PPI network diagrams and imported into CytoScape 3.7.1 to obtain the potential key target genes,and then the KEGG pathway analysis was performed on the key target genes.Sixty SD rats were randomly divided into blank group,model group,colchicine group and QFZTS high-,medium- and low dose-group.AGA model was established by intra-articular injection of monosodium urate (MSU) suspension in the ankle joint in all groups except for the blank group.Histopathological changes in the synovial membrane of the ankle joint were observed by hematoxylin-eosin (HE) staining.The serum levels of interleukin (IL)-1β,IL-6,tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 were measured by enzyme-linked immunosorbent assay (ELISA).RT-qP-CR was employed to detect the mRNA expression of NLRP3,Caspase-1 and IL-1β in the soft tissue around the ankle joint.Results:The top 20 targets of QFZTS with the highest correlation to AGA were MAPK14、CXCL8、CRP、IL-1β、NLRP3、CASP1、IL-6、TNF and TGF-β1,among which inflammatory factors played an important role.Compared with the model group,the serum levels of IL-1β,IL-6,TNF-α and TGF-β1 were reduced in the QFZTS high-dose group,the mRNA expression of NLRP3,Caspase-1 and IL-1β in the soft tissue around the ankle joint was down-regulated in the QFZTS high and medium-dose group (P<0.05),the synovial proliferation was improved to different degrees,and inflammatory cell infiltration was reduced.Conclusion:QFZTS may inhibit AGA by down- regulating inflammator

关 键 词：驱风止痛散 网络药理学 急性痛风性关节炎 

分 类 号：R589.7[医药卫生—内分泌]