化瘀通痹方从瘀论治类风湿关节炎的肠道微生态调节机制

DMARDs is a first-line drug in the treatment of rheumatoid arthritis, which may bring about lots of toxic or side-effects after long-term used, included the cumulative decline in efficacy, infection and other secondary diseases. Our team focused on treating RA by promoting blood circulation by removing blood stasis for more than 20 years. Based on the clinical experience and research results, correlated the academic.idea that “blood stasis throughout the whole pathogenesis of RA”, combined with the academic thought of Chinese medicine master Zhu Liangchun in the treatment of Wangbi's, after repeated demonstration and refining, the Huayu-Tongbi Decoction (HQT Decoction) was created. The efficacy, safety and stability of HQT Decoction and the combination of HQT Decoctionand MTX have been confirmed through the study of the clinical effect and the mechanism of animal pharmacodynamics. However, as the traditional Chinese medicine prescription, the way of how to exert its effect is always difficult to clarify, limiting its popularization and application and long-term development. This study is seek to identify the role of intestinal microflora in the mechanism of HQT Decoction and the combination of HQT Decoction and MTX by using high-throughput sequencing and bioinformatics analysis, combined with the research and evaluation of animal pharmacodynamic mechanism of clinical efficacy. And subsequently clarify the mechanism of promoting blood circulation removing blood stasis in treating RA.

改善病情抗风湿药（DMARDs）是治疗类风湿关节炎的一线药物，但长期使用存在毒副作用累积、疗效稳定性下降、诱发感染和继发疾病等问题。本团队根据20多年“活血化瘀法”治疗RA的临床经验和研究成果，基于“血瘀贯穿痹病始末”的病机认识，结合中医经典与国医大师朱良春治疗尪痹的学术思想，经过反复论证，提炼、创制“化瘀通痹方”。前期已通过临床疗效以及动物药效机制研究肯定了化瘀通痹方及其联合MTX的中西医结合方案的有效性，安全性和稳定性。然而化瘀通痹方与其他中药复方一样，其发挥疗效的途径是如何始终难以阐明，限制其推广运用和长远发展。本研究拟从肠道微生态入手，借助高通量测序以及生物信息学分析，结合临床疗效评价和动物药效机制研究，多层面系统的探讨“化瘀通痹方”从瘀论治类风湿关节炎的肠道微生态物质基础，并在该层面上进一步明确活血化瘀法在治痹中的作用和机制。

改善病情抗风湿药（DMARDs）是治疗类风湿关节炎（rheumatoid arthritis，RA）的一线药物，但长期使用存在毒副作用累积、疗效稳定性下降、诱发感染和继发疾病等问题。本研究从肠道微生态入手，借助高通量测序以及生物信息学分析，结合临床疗效评价和动物药效机制研究，多层面系统的探讨“化瘀强肾通痹方”从瘀论治RA的肠道微生态物质基础，并在该层面上进一步明确活血化瘀法在治痹中的作用和机制。临床疗效评价研究方面，研究比较了化瘀强肾通痹方联合甲氨蝶呤(MTX)与MTX联合来氟米特(LEF)治疗活动性RA患者的疗效和安全性，发现化瘀强肾通痹方+MTX组和MTX+LEF组疗效相当，具有良好的临床疗效，这可能与体征、症状和身体功能的改善有关，化瘀强肾通痹方联合MTX是治疗RA的另一种良好治疗方案；肠道微生态研究方面，研究发现接受化瘀强肾通痹方或LEF治疗的RA患者肠道微生物组和健康对照之间的肠道微生物组存在差异，这些结果为肠道菌群在RA发病机制中的作用提供了研究基础，也为开发新的RA治疗提供了潜在的研究方向；动物药效机制研究方面，我们检测了各项相关免疫系统指标和收集实验D0和D30天大鼠粪便进行了16S分析，研究发现化瘀强肾通痹方潜在靶标菌群对大鼠免疫系统的发育和激活具有一定的影响，至少一部分功能是通过抑制靶标菌群而发挥抗炎疗效，研究结果将进一步促进化瘀强肾通痹方对肠道菌群机制的开发应用。