痹祺胶囊治疗类风湿性关节炎的药效研究及网络机制预测  

Pharmacodynamic study and network mechanism prediction of Biqi Capsule in treatment of rheumatoid arthritis

作　　者：李新 卜睿臻 王玉丽[1,2,3] 李虎玲 韩彦琪[1,2,3] 王磊 张星艳[1,2,3] 赵文静[1,2,3] 许浚[1,2,3] 张铁军[1,2,3] 刘昌孝[1,2,3] LI Xin;BU Rui-zhen;WANG Yu-li;LI Hu-ling;HAN Yan-qi;WANG Lei;ZHANG Xing-yan;ZHAO Wen-jing;XU Jun;ZHANG Tie-jun;LIU Chang-xiao(Tianjin Key Laboratory of Quality Marker of Traditional Chinese Medicine,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;National&Local United Engineering Laboratory of Modern Preparation and Quality Control Technology of Traditional Chinese Medicine,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;Tianjin Darentang Jingwanhong Pharmaceutical Co.,Ltd.,Tianjin 300112,China;Tianjin Pharmaceutical Da Ren Tang Group Co.,Ltd.,Tianjin 300193,China)

机构地区：[1]天津药物研究院,天津市中药质量标志物重点实验室,天津300462 [2]天津药物研究院,中药现代制剂与质量控制技术国家地方联合工程实验室,天津300462 [3]天津药物研究院,药物成药性评价与系统转化全国重点实验室,天津300462 [4]天津达仁堂京万红药业有限公司,天津300112 [5]津药达仁堂集团股份有限公司,天津300193

出　　处：《中草药》2023年第23期7618-7629,共12页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金重点项目(U21A20406)。

摘　　要：目的 基于Ⅱ型胶原诱导的类风湿性关节炎(rheumatoid arthritis,RA)大鼠模型和网络药理学方法探讨痹祺胶囊的药效作用及作用机制。方法 SD大鼠采用Ⅱ型胶原蛋白造模,造模成功大鼠随机分为模型组,痹祺胶囊(0.05、0.10、0.20、0.40 g/kg)组及泼尼松(10 mg/kg)组和雷公藤总苷(10 mg/kg)组,连续给药15 d。持续监测大鼠体质量、足趾肿胀度和关节炎评分,苏木素-伊红染色考察大鼠踝关节病理变化,ELISA法测定血清细胞因子含量,初步评价痹祺胶囊治疗效果。选择痹祺胶囊中39个化合物为研究对象,依据反向药效团匹配方法和TCMSP、Uniprot等数据库预测化合物作用靶点,与通过OMIM、Dis Ge Net等数据库收集的RA相关靶点相互交互,将交互靶点借助Omicsbean、STRING等数据库平台对获得靶点进行基因本体功能和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,利用Cytoscape软件构建“药材-化合物-靶点-通路-功效-疾病”网络,预测其可能的作用机制。结果 与对照组比较,模型组大鼠活动、饮食减少,足趾肿胀、关节呈急性炎症表现,关节炎评分显著增加(P<0.01),血清中类风湿因子(rheumatoid factor,RF)、白细胞介素-17(interleukin-17,IL-17)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、IL-1β和γ-干扰素(interferon-γ,IFN-γ)水平均显著增加(P<0.05、0.01、0.001),IL-10水平降低,脾脏、胸腺指数显著增加(P<0.01、0.001),病理显示膝关节可见滑膜细胞增生、炎性细胞浸润,骨与软骨被侵蚀。与模型组比较,痹祺胶囊组大鼠踝关节病变情况得到不同程度改善,具体可见足肿胀度、关节炎评分显著降低(P<0.05、0.01),血清中RF、IL-17、TNF-α、IL-1β、IFN-γ水平显著降低(P<0.05、0.01、0.001),IL-10水平增高,脾脏、胸腺指数降低(P<0.05、0.01),踝关节骨、软骨组织损伤减轻,炎性细胞浸润、滑膜结缔组织增生减少。网�Objective To explore the pharmacodynamic effect and potential mechanism of Biqi Capsule(痹祺胶囊)based on typeⅡcollagen-induced rheumatoid arthritis(RA)rat model and network pharmacology.Methods SD rats were modeled with type Ⅱ collagen,and the successful rats were randomly divided into model group,Biqi Capsule(0.05,0.10,0.20,0.40 g/kg)groups,prednison(10 mg/kg)group and Trjpterygium glycosides(10 mg/kg)group.Rats were continuously ig for 15 d,body weight,foot swelling and arthritis score of rats were continuously monitored.Hematoxylin-eosin staining was used to observe the pathological changes of ankle joint in rats,and the content of cytokines in serum was determined by ELISA,so as to preliminarily evaluate the therapeutic effect of Biqi Capsule.A total of 39 compounds in Biqi Capsule were selected as the research objects,and the targets of the compounds were predicted according to the reverse pharmacophore matching method and databases such as TCMSP and Uniprot.With the help of database platforms such as Omicsbean,STRING,etc.,the interactive targets were analyzed by gene ontology function and Kyoto encyclopedia of genes and genomes(KEGG)pathway by interacting with RA-related targets collected through OMIM,DisGeNet and GeneCards,and“medicinal materialcompound-target-pathway-efficacy-disease”network was constructed by Cytoscape software to predict its possible mechanism.Results Compared with control group,the activity and diet of rats in model group were reduced,the toes were swollen,the joints showed acute inflammation,the arthritis score was significantly increased(P<0.01),and the levels of rheumatoid factor(RF),interleukin-17(IL-17),tumor necrosis factor-α(TNF-α),IL-1βand interferon-γ(IFN-γ)in serum were significantly increased(P<0.05,0.01,0.001),while the level of IL-10 was decreased,indexes of spleen and thymus were increased(P<0.01,0.001).Pathology showed that synovial cells were proliferated,inflammatory cells were infiltrated and bone and cartilage were eroded.Compared with model group,t

关 键 词：痹祺胶囊 类风湿关节炎 免疫调节 血管增生 炎症 镇痛 士的宁 三七皂苷R_(1) 人参皂苷Rg_(1) 丹参酮Ⅰ 丹参酮Ⅱ_(A) 丹酚酸B 异甘草素 迷迭香酸 阿魏酸 

分 类 号：R285.5[医药卫生—中药学]