雷公藤联合甲氨蝶呤治疗类风湿性关节炎的meta分析及生物信息学研究

发布时间：2018-07-31 05:24

【摘要】：目的雷公藤联合甲氨蝶呤已经被广泛应用于类风湿性关节炎(Rheumatoid arthritis,RA)的治疗,但是该联合用药策略的安全性和有效性还不是很清楚。本研究希望利用meta分析考察该治疗方法的安全性和有效性,并进一步利用生物信息学初步研究其潜在的作用机制。方法Meta分析研究:在中英文数据库(中国知网、维普、万方、Pubmed和Web of Science)中全面检索雷公藤联合甲氨蝶呤治疗RA的文献研究,按照规定的标准对这些文献进行筛选以及相关数据的提取和分析,对雷公藤联合甲氨蝶呤的有效性和安全性进行分析。信息学研究:从TCMID数据库中搜索雷公藤相关作用靶点;从OMIM、GAD、KEGG中搜索RA疾病的相关基因;从DrugBank和Pharmainformatics数据库中搜索治疗RA的药物相关作用靶点。对所获得的这些基因和靶点进行比较分析,寻找共同的作用靶点和相关信号通路。综合分析结果,对雷公藤联合甲氨蝶呤治疗RA可能的作用机制进行研究。结果1、通过对符合纳入标准的6篇(共计643例患者)联合用药的随机对照研究进行meta分析,我们发现,疗效方面,联合雷公藤可提高50%的响应率(RR 1.337,95%CI:1.188-1.505,P0.001),并缩短晨僵时间、减少疼痛和肿胀关节数、降低红细胞沉降率、降低C反应蛋白表达、减少类风湿性因子;安全性方面,合用雷公藤多苷不增加不良反应发生率(RR 0.824,95%CI:0.635-1.068,P=0.143)。2、通过对雷公藤所含成分和甲氨蝶呤的作用靶点、其他抗RA药物作用靶点以及RA相关基因进行生物信息学分析,我们发现雷公藤和甲氨蝶呤可能存在5个共同的作用靶点,并且雷公藤和甲氨蝶呤可能共同作用于淋巴细胞增殖相关信号通路。另外雷公藤还可能单独调节免疫系统的其他三条RA相关的信号通路(调节单核细胞、TLR1:TLR2信号通路、干扰素γ信号通路)。结论目前的研究初步表明雷公藤联合甲氨蝶呤相较于单独应用甲氨蝶呤可能是一种安全有效的治疗策略,并且生物信息学研究为该用药方式的有效性提供理论证据。当然,雷公藤联合甲氨蝶呤的长期效应以及安全性还需要进一步的研究。
[Abstract]:Objective Tripterygium wilfordii combined with methotrexate has been widely used in the treatment of rheumatoid arthritis (Rheumatoid arthritis RA). The purpose of this study is to investigate the safety and efficacy of this treatment by meta analysis and to further study its potential mechanism by bioinformatics. Methods Meta analysis: the literature of Tripterygium wilfordii combined with methotrexate in the treatment of RA was searched in Chinese and English databases. The efficacy and safety of tripterygium wilfordii combined with methotrexate were analyzed by screening these documents and extracting and analyzing relevant data according to the prescribed standards. Informatics: search for tripterygium wilfordii related targets from TCMID database; search for genes related to RA disease from OMIMN GADKEGG; search for drug related targets for RA treatment from DrugBank and Pharmainformatics databases. These genes and targets were compared and analyzed to find common targets and related signaling pathways. The possible mechanism of Tripterygium wilfordii combined with methotrexate in the treatment of RA was studied. Results 1. By meta analysis of 6 randomized controlled trials (643 patients), we found that the response rate of tripterygium wilfordii combined with tripterygium wilfordii was increased by 50% (RR 1.33795 CI: 1.188-1.505P0.001), and the time of morning stiffness was shortened. Reduce pain and swelling joint number, reduce erythrocyte sedimentation rate, reduce C-reactive protein expression, reduce rheumatoid factor; safety, The combination of tripterygium wilfordii polyglycosides did not increase the incidence of adverse reactions (RR 0.824 ~ 95CI: 0.635-1.068) 0.143. The bioinformatics analysis was carried out on the components of Tripterygium wilfordii and the target of methotrexate, other anti-RA drug targets and RA related genes. We found that Tripterygium wilfordii and methotrexate may have five common targets and that Tripterygium wilfordii and methotrexate may work together on the lymphocyte proliferation-related signaling pathway. In addition, Tripterygium wilfordii may regulate three other RA-related signaling pathways in the immune system alone (regulation of monocyte TLR1: TLR2 signaling pathway, interferon 纬 signaling pathway). Conclusion the present studies suggest that tripterygium wilfordii combined with methotrexate may be a safe and effective therapeutic strategy compared with that of methotrexate alone, and bioinformatics studies provide theoretical evidence for the efficacy of this method. Of course, the long-term effects and safety of tripterygium wilfordii combined with methotrexate need further study.
【学位授予单位】：浙江中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.22

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