基于VEGF/NLRP3通路探讨新痹通灵抑制RA异常血管新生的机制

类风湿关节炎（RA）是一种发病率较高、易致残的风湿免疫病，为家庭和社会带来巨大的经济负担。已故著名中医风湿病学家汪履秋先生根据RA发病特点，提出该病主要病机为“风寒久羁，经闭络阻”，治当发散风寒，剔络通痹。学术继承人汪悦教授及其课题组根据汪老经验不断优化，形成“新痹通灵”复方，已有数十年临床使用及研究历史，临床疗效显著；并进一步提出“病络缠绊”的病机，与RA异常血管新生和血管翳形成存在联系。课题组前期研究表明，该方可缓解关节炎症，减少异常血管新生，对VEGF、IL1-β等在内的多个靶点产生影响，但具体机制不明。NLRP3是介导IL-1β释放的关键因子，且受到VEGF调控，因此本研究中，我们试图从VEGF/NLRP3/IL-1β通路探讨新痹通灵对RA异常血管新生的抑制，希望进一步揭示新痹通灵对RA治疗的作用机制，同时为抗风湿中药的新药研究提供研究基础和依据。

Rheumatoid arthritis (RA) is a rheumatic immune disease with high incidence and disability, which brings a vast economic burden to the family and society. According to the characteristics of RA, the late famous rheumatologist in traditional Chinese medicine (TCM) Mr. Wang Lvqiu put forward that the main pathogenesis of RA is "the blockage in meridian and stasis in collateral caused by long-term detention of wind and cold", which should be treated as dispersing wind-cold, unblocking collaterals and removing impediment. Professor Wang Yue, the academic successor, and his research team have been optimizing constantly according to former Wang's experience to form the "Xinbitongling" compound, which has been used and studied for decades and has a remarkable clinical effect; furthermore, they put forward the pathogenesis of "entwining of diseased collaterals", which is consistent with the clinical feature of abnormal angiogenesis and formation of pannus in RA. Previous studies have shown that this formula can alleviate arthritis, reduce abnormal angiogenesis, and affect multiple targets such as vascular endothelial growth factor (VEGF) and interleukin-1 beta (IL-1β), but the specific mechanism is unclear. NLRP3 is a key factor mediating the release of IL-1β and is regulated by VEGF. In this study, we attempt to explore the inhibition of Xinbitongling on angiogenesis in RA through the pathway of VEGF/NLRP3/IL-1β. We hope to further reveal the mechanism of Xinbitongling on the treatment of RA, and also provide foundation and basis for the study of new anti-rheumatic drugs in TCM.