杨俊;李泰贤;王晓月;薛志鹏;吕诚;李慧珍;樊媛芳;李逸群;田雅格;陈文佳;郭敏群;王靖霞;吴红艳;张彦琼;朱春燕;林娜;
YANG Jun;LI Tai-xian;WANG Xiao-yue;XUE Zhi-peng;LYU Cheng;LI Hui-zhen;FAN Yuan-fang;LI Yi-qun;TIAN Ya-ge;CHEN Wen-jia;GUO Min-qun;WANG Jing-xia;WU Hong-yan;ZHANG Yan-qiong;ZHU Chun-yan;LIN Na;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences;Wangjing Hospital, China Academy of Chinese Medical Sciences;Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences;

• 1:中国中医科学院中药研究所
• 2:中国中医科学院望京医院
• 3:中国中医科学院中医临床基础研究所

摘要(Abstract)：

系统评价雷公藤多苷(甙)片单独或联合甲氨蝶呤(MTX)、来氟米特(LEF)使用对类风湿关节炎(RA)患者或动物模型体内促炎细胞因子水平的影响,为临床应用和相关基础研究提供参考。该研究通过系统检索中国知网、维普、万方、PubMed、Embase、Cochrane Library等数据库,收集相关临床或动物实验研究,采用风险评估工具进行研究质量评价,使用Revman 5.3软件对纳入文献的结局指标进行Meta分析或描述性分析。在检索到的1 709篇文献中,该文最终纳入3篇临床研究和12篇动物实验研究。分析结果显示,在RA患者体内,与单用MTX相比,雷公藤多苷(甙)片联合MTX能进一步降低外周血TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01)、IL-1β(P<0.000 01)、IL-6(SMD=-8.63,95%CI[-10.57,-6.69],P<0.000 01)的表达水平;与单用LEF相比,雷公藤多苷(甙)片联合LEF未能进一步降低外周血TNF-α(P=0.20)、IL-1β(P=0.17)、IL-6(P=0.31)的表达水平。在RA动物模型体内,与模型组相比,雷公藤多苷(甙)片能降低外周血(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01)、关节液(P<0.000 01)及足爪研浆(P=0.02)TNF-α的表达水平,并降低外周血IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],P=0.000 2)表达水平;与单用MTX相比,单用雷公藤多苷(甙)片降低关节液TNF-α(P=0.42)、IL-6(P=0.08)表达水平的作用相当,雷公藤多苷(甙)片联合MTX能进一步降低关节液IL-6(P=0.000 1)表达水平;与单用LEF相比,雷公藤多苷(甙)片降低外周血TNF-α(P=0.16)、IL-1β(P=0.32)、IL-6(P=0.12)表达水平的作用相当,雷公藤多苷(甙)片联合LEF能进一步降低外周血TNF-α(P=0.008)、IL-1β(P=0.02)、IL-6(P<0.000 1)的表达水平。因此,雷公藤多苷(甙)片联合MTX使用能进一步降低RA患者的外周血促炎细胞因子表达水平;雷公藤多苷(甙)片单用能够降低RA动物模型外周血及关节局部的促炎细胞因子表达水平;雷公藤多苷(甙)片联合MTX或LEF使用能进一步降低RA动物模型的外周血促炎细胞因子的表达水平。因纳入文献的限制,该结论还有待进一步验证。
To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1β(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1β(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1β(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1β(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.

关键词(KeyWords)： 类风湿关节炎;雷公藤多苷(甙)片;系统评价;促炎细胞因子
rheumatoid arthritis;Tripterygium Glycosides Tablets;systematic review;pro-inflammatory factors

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81974526);; 北京市自然科学基金项目(7192139);; 中国中医科学院中医药“一带一路”合作专项(GH2017-06)

作者(Authors): 杨俊;李泰贤;王晓月;薛志鹏;吕诚;李慧珍;樊媛芳;李逸群;田雅格;陈文佳;郭敏群;王靖霞;吴红艳;张彦琼;朱春燕;林娜;
YANG Jun;LI Tai-xian;WANG Xiao-yue;XUE Zhi-peng;LYU Cheng;LI Hui-zhen;FAN Yuan-fang;LI Yi-qun;TIAN Ya-ge;CHEN Wen-jia;GUO Min-qun;WANG Jing-xia;WU Hong-yan;ZHANG Yan-qiong;ZHU Chun-yan;LIN Na;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences;Wangjing Hospital, China Academy of Chinese Medical Sciences;Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences;

DOI: 10.19540/j.cnki.cjcmm.20191024.401

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