基于“以方测证”的类风湿关节炎风寒湿痹证 动物模型的构建研究

林也 戴宗顺 张婷 张逢 胡胜涛 张二兵 宋厚盼 陈聪 蔡雄 廖菁

〔摘要〕 目的 基于以方測证理论建立与类风湿关节炎（RA）病变特征、发病机制相符的中医“痹证”动物模型。方法 将40只雄性SD大鼠随机分为空白组、风寒湿痹证模型组、风寒湿痹证模型+乌头汤组（乌头汤组）、风寒湿痹证模型+四妙丸组（四妙丸组），每组10只大鼠。空白组大鼠无任何干预措施，余各组大鼠均先予以风寒湿环境刺激14 d，再诱导建立佐剂性关节炎（AIA）大鼠模型，同时乌头汤组与四妙丸组分别给予乌头汤和四妙丸灌胃治疗，直至实验结束。记录各组大鼠发病时间和发病率;动态检测大鼠足肿胀体积和评价关节炎指数积分;HE染色观察大鼠踝关节病理变化;CT检测大鼠骨关节破环情况。结果 与风寒湿痹证模型组比较，乌头汤明显延迟大鼠发病时间并降低其发病率，显著减轻大鼠关节肿胀率及关节炎指数评分，明显抑制滑膜组织增生及骨破坏程度（P<0.01），而四妙丸组大鼠病变程度与风寒湿痹证模型组无明显差别（P>0.05）。结论 基于以方测证思路，成功复制了与RA病变特征和发病机制相符的RA风寒湿痹病证结合大鼠模型，为系统深入研究治疗RA方证对应分子机制奠定了基础。

〔关键词〕 类风湿关节炎;风湿痹证;方证对应;佐剂性关节炎;乌头汤;四妙丸

〔中图分类号〕R285.5       〔文献标志码〕A       〔文章编号〕doi：10.3969/j.issn.1674-070X.2021.05.003

Construction of Animal Model of Rheumatoid Arthritis with Wind Cold Dampness Arthralgia Syndrome Based on the Theory of "Testing Syndrome by Formula"

LIN Ye1， DAI Zongshun2， ZHANG Ting1， ZHANG Feng1， HU Shengtao1， ZHANG Erbing1， SONG Houpan2，

CHEN Cong2， CAI Xiong1*， LIAO Jing2*

（1. Institute of Innovation and Applied Research in Chinese Medicine， Hunan University of Chinese Medicine， Changsha，

Hunan 410208， China; 2. Hunan Provincial Key Laboratory of Translational Research in TCM Formulas and Zheng，

Hunan University of Chinese Medicine， Changsha， Hunan 410208， China）

〔Abstract〕 Objective To establish an animal model of "arthralgia syndrome" in traditional Chinese medicine （TCM） based on the theory of testing syndrome by formula， which was consistent with the pathological characteristics and pathogenesis of rheumatoid arthritis （RA）. Methods 40 male Sprague-Dawely （SD） rats were randomly assigned into the blank group， the wind cold dampness arthralgia syndrome model group， wind cold dampness arthralgia syndrome model+Wutou Decoction group， wind cold dampness arthralgia syndrome model+Simiao Pill group， with 10 rats in each group. There was no intervention in the blank group， the rats in other groups were stimulated by wind， cold and wet environment for 14 days， and then induced to establish adjuvant arthritis （AIA） rat model. At the same time， the wind cold dampness arthralgia syndrome model+Wutou Decoction group， wind cold dampness arthralgia syndrome model+Simiao Pill group were given Wutou Decoction and Simiao Pill by gavage until the end of the experiment. The onset time and incidence rate of rats were recorded. Foot swelling volume and arthritis index score were measured dynamically. HE staining was used to observe the pathological changes of the ankle joint in rats. CT was used to detect the fracture of bone and joint in rats. Results Compared with the wind cold dampness arthralgia syndrome model group， Wutou Decoction significantly delayed the onset time of rats and reduce the incidence of a disease， significantly reduce index score， joint swelling rate and arthritis of rats significantly inhibit the synovial tissue and bone damage （P<0.01）， and the lesion degree of wind cold dampness arthralgia syndrome model+Simiao Pill group and the wind cold dampness arthralgia syndrome model group was no significant difference （P>0.05）. Conclusion Based onthe theory of testing syndrome by formula， we successfully reproduce the characteristics and pathogenesis of RA and pathological changes of RA wind cold dampness arthralgia syndrome in the rat model of combined disease for system in-depth study in the treatment of RA certificate corresponding to molecular mechanism laid a foundation.

〔Keywords〕 rheumatoid arthritis; wind cold dampness arthralgia syndrome; correspondence of formula-Zheng; adjuvant-induced arthritis; Wutou Decoction; Simiao Pill

类风湿关节炎（rheumatoid arthritis， RA）是一种以慢性侵蚀性关节炎为主要特征的自身免疫性疾病，其临床表现为多关节反复发炎，缠绵难愈，滑膜细胞“类肿瘤生长”，有不死的癌症之称，为临床难治性疾病之一[1-3]。……