【作者】 任璇璇；

【导师】 宋欣伟；

【作者基本信息】 浙江中医药大学 ， 中医内科学， 2014， 博士

【摘要】 本研究包括三方面内容,①理论部分：整理古代有关“痹证”文献并总结分昕宋师提出的“伏邪晚发致痹”学术思想。②临床部分：系统观察类风湿I号治序活动期RA的临床疗效,并进行安全性评价。③实验部分：观察活动期RA血清中JAK-STAT蛋白与NEI网络因子的表达,并观察类风湿I号对相关蛋白及因子的影响,从而为进一步探讨类风湿I号的作用机理提供依据。方法①理论部分：通过整理古代文献,挖掘宋师“伏邪晚发致痹”学术思想理论渊源。②临床部分：选择符合2009年ACR有关RA分类标准的活动期RA患者90例,随机分组,治疗组予类风湿I号联合雷公藤多甙片治疗,对照组予雷公藤多甙片治疗,观察周期为12周。观察两组患者ACR及DAS28变化,评价其临床疗效及安全性。主要观察指标包括：疼痛关节数、肿胀关节数、关节疼痛(VAS评分)、晨僵时间、双手握力及ESR、CRP、RF、CCP及血常规、肝功能等。③实验部分：选择活动期RA患者40例,将40例RA患者随机分为2组,分别予类风湿I号联合雷公藤多甙片和单纯雷公藤多甙片治疗,观察周期为12周,用ELISA法测定RA患者治疗前后血清中JAK1、STAT3、IL-6、IL-21、 SP及PRL的浓度,并与健康对照者20例比较,分析RA患者治疗前后血清中6指标的变化。结果①理论部分：总结宋师提出“伏邪晚发致痹”学术思想理论渊源,宋师认为脾气亏虚、湿热痰瘀痹阻是活动期RA的核心病机,提出从复法大方治痹的治疗原则,自创类风湿I号并运用于临床。②临床部分：类风湿I号治疗活动期RA疗效明显,DAS28总有效率为93.33%；100%达ACR20,77.78%达ACR50,42.22%达ACR70。临床症状方面,类风湿I号不仅能明显改善晨僵时间、双手握力,减少关节疼痛数目和肿胀数目还能明显降低CRP、ESR、抗CCP抗体水平,而且安全性高,无明显毒副作用。③实验部分：活动期RA患者JAK1,STAT3, IL-6, IL-21, SP及PRL血清浓度水平显著高于健康对照组。治疗活动期RA12周后,RA对照组和治疗组6因子浓度均有不同程度的下调,且治疗组在IL,-6、JAK1、STAT3及SP下降更明显。结论类风湿I号是宋师基于“伏邪晚发致痹”及“脾气亏虚、湿热痰瘀痹阻”是活动期RA的核心病机等学术思想所创的中药复方；类风湿I号能显著改善活动期RA的临床症状,降低炎症活动实验室指标,且不良反应小；类风湿关节炎活动期,JAK-STAT信号通路和神经内分泌免疫网络处于激活状态,类风湿I号可抑制JAK-STAT信号通路蛋白和NEI网络因子的表达。更多还原

【Abstract】 Objective This subject include three parts.①Theoriest part,I learn formed form TCM classic theories and my tutor get the knowledge that as "hidden-pathogens causing rheumatism doctrine"②Clinical part, systematic evaluate and compare the therapeutic efficacy of Rheumatoid one in treating activated arthritis to evaluate the clinical effect and drug-using security.③Experiment research,we using the serum of RA patient,testing the level of JAK-STAT proteins and some factors of NEI network,then to observe the effect of Rheumatoid one to them,in order to provide the basis of the mechanism of this drug worked on arthritis.Methods①Theoriest part, by collectting the TCM classic theories,we found the origin theory of the knowledge "hidden-pathogens causing rheumatism doctrine".②Clinic Part:By American College Rheumatology(ACR)standard classification of2009for diagnosis basis.Ninety patients of RA were randomly divided into two group.The treatment group treated with Rheumatoid one Combined With Tripterygium wilfordii while the control group only treated withTripterygium wilfordii. The treatment of12weeks was observed in the Patients with the difference of ACR and DAS28to evaluated its clinical efficacy.Main outcome measures:include tender joint count,swellon joints count,pain joint count,visual analogue scale test,time of morning stiffness(min),hand grip strength (mmHg) and ESR,CRP,RF,a-CCP, PLT,RBC,WBC,HGB,ALT,AST.③Experiment research:we choose forty patients whose disease at the activity time, then randomly divided the forty patients into two groups as the treatment group which treated with Rheumatoid one Combined With Tripterygium wilfordii while the control group only treated with Tripterygium wilfordii. Using ELIS A method for the determination of serum JAK1,STAT3,IL-6, IL-21,SP,PRL.The observe time is twelve weeks. Meanwhile, we choose twenty healthy people as controls,. observe the change of six indexes in the serum,and compare the after-treating indexes with the before-treating in activity RA.Results①Theoriest part, We think that main pathology mechanism of RA in periods of activity is low-speel function, damp-heat and stasis-toxicant obstructing channels and flowing to limbs joints. We work form complex way and large amount of the medicine making the drug called Rheumatoid one.②Clinic Part:after treatment for3months, the treatment group got a better overall assessment, The total effective rate of DAS28is93.3%,all patients got ACR20,77.8%patients got ACR50and42.22%patients got ACR70.Signs and symptoms aspect:Rheumatoid one play a good role not only on relieve the pain and swelling, morning stiffness, grip strength, pain VAS score and patient overall health status and also show at blood indicators:ESR, CRP, RF and a-CCP have varying degrees of decline after treatment. Meanwhile Rheumatoid one have low adverse effects, no adverse effects of combination therapy superposition.③Experiment research:the serum of JAK1,STAT3,IL-6,IL-21,SP, PRL which owed by activity RA is higher than healthy ones.After treatment,both groups make these factors low in different extent,and the group with Rheumatoid one get more obvious low in IL-6,JAK1,STAT3and SP.Conclusion Rheumatoid one is an origin theory based on my tearchers academic thought; It can significantly alleviate the clinical symptoms of patients, significantly reduce laboratory index,and have less adverse reaction;Being activity RA,the JAK-STAT load and NEI network is being actived, Rheumatoid one can partially inhibit the activation of JAK-STAT protein and NEI network factor.更多还原