基于祛风湿功效的平性中药秦艽寒热不同配伍药对对RA大鼠作用性-效关系研究

Rheumatoid arthritis ( RA ) belongs to the category of arthralgia in Traditional Chinese medicine. It is treated clinically by means of expelling wind and removing dampness, dredging the collateral channels to kill pain, invigorating kidney and activating blood circulation, etc. The herbs for wind expelling and dampness removing should be first select to treat the disease. The key point to be studied for prescription making is matching the cold and hot herbs with the function of wind expelling and dampness removing. Directed by this theory and on the basis of previous research, it i proposed that the mild Gentiana macrophylla should be taken as the basic medicine to form the pair of mild to mild ( Gentiana + Taxillus chinensis ), mild to cold (Gentiana + Radix Stephaniae Tetrandrae), mild to temperate( Gentiana + Radix Clematidis), which have different effect on the RA. RA rat syndrome model of wind-cold-damp and wind-damp-hot arthralgia will be established with collagen II protein induction and wind-cold-damp or wind-damp-hot environmental factors. The quantitative evaluation of general state, joint inflammation, joint histomorphology of rat model, combined with immune organ index and the detection of peripheral blood CRP, RF, TNF- α, IL-1, PGE2 levels, will be done and the compatibility of wind-cold-dampness arthralgia and wind-damp-hot arthralgia rat model will be comprehensively analyzed in the relation of cold, hot, mild herb match and syndrome of disease. The connections among the property of traditional Chinese herbs, syndrome of disease and effect will be explained. Ideas and methods of property research based on the traditional function of Chinese medicine will be explored.

类风湿性关节炎(RA)属于中医"痹证"范畴，临床多采用祛风除湿、通络止痛、补肾活血等治法，首选祛风湿药。具有祛风湿功效而寒热药性不同的中药配伍使用是组方用药的关键和研究重点，以此为理论指导，在前期研究的基础上，提出以平性中药秦艽为基本药，组成平-平相配（秦艽+桑寄生）、平-寒相配（秦艽+防己）、平-温相配（秦艽+威灵仙）的配伍药对对RA具有不同疗效的假说，采用Ⅱ型胶原蛋白诱导并附加风寒湿或风湿热的环境因素，分别构建符合中医"痹证"特点的病证结合风寒湿痹和风湿热痹RA大鼠模型，进行模型大鼠一般状态、关节炎症、关节组织形态学的定量评价，结合免疫脏器指数及外周血CRP、RF、TNF-α、IL-1、PGE2的水平检测，综合分析风寒湿痹和风湿热痹RA大鼠模型中，寒、热、平药性配伍与病证之间的适从性，阐释中药药性-病证-疗效之间的关联性，探索建立基于传统功用的中药药性研究的思路与方法。

1）研究采用Ⅱ型胶原蛋白诱导，附加人工气候箱模拟自然环境中风、寒、湿、热的刺激，分别构建了符合中医“痹证”特点的病证结合的风寒湿痹和风湿热痹RA大鼠模型。结果无论是风寒湿痹RA模型，还是风湿热痹RA模型，均比单纯Ⅱ型胶原所造RA疾病模型病情严重，病程长，符合痹证“缠绵难愈”的临床特点。.2）研究基于祛风湿功效，以平性中药秦艽为基本药，分别配伍威灵仙、桑寄生、防己，组成平温相配（秦艽+威灵仙）、平平相配（秦艽+桑寄生）、平寒相配（秦艽+防己）的配伍药对，分别作用于风寒湿痹和风湿热痹RA模型大鼠。从足跖肿胀度，AI评分，踝关节组织病理学变化，X线片改变，免疫脏器指数比较，ESR变化，血清RF、CRP、TNF-α、IL-1β、PGE2、抗CCP抗体检测及WB技术检测踝关节VEGF、NF-κB的表达量等多方面分析寒、热、平不同药性配伍药对与风寒湿痹和风湿热痹病证之间的性效关系。综合实验结果，对风寒湿痹RA大鼠的疗效趋势为：秦威组(平温相配)＞秦桑组(平平相配)＞单味秦艽组＞秦防组(平寒相配)，其中平温相配治疗效果较为突出，平平相配作用次之，平寒相配作用更次，体现了“热性药-寒证-疗效佳”的辨证关系，符合中医“寒者热之”“疗寒以热药”的用药原则；对风湿热痹RA大鼠的疗效趋势为：秦防组(平寒相配)＞秦威组(平温相配)＞秦桑组(平平相配)＞单味秦艽组，其中平寒相配治疗效果较为突出，平温相配作用次之，平平相配作用更次，体现了“寒性药-热证-疗效佳”的辨证关系，符合中医“热者寒之”“疗热以寒药”的用药原则。.3）在风湿热痹中，平温相配仅次于平寒相配，而优于平平相配，说明寒、热药性突显的中药作用较强，而寒热药性不显著的平性药作用和缓。.4）在所造痹证模型中，无论是风寒湿痹，还是风湿热痹，平温相配均显示出较好的疗效，说明痹证的治疗应以“温通”为用；剂量相同情况下，秦桑组(平平相配)的疗效优于单味秦艽组(平性)，说明中药配伍应用优于单味药。.5）在多批次的动物实验中，均发现中药组大鼠较其他组的尿液多，尤其是单味秦艽组。经查阅文献，《神农本草经》明确记载秦艽有“下水，利小便”作用，《药性论》《药类法象》也有“利小便”功效的记载。但不知何时起，利小便作用被弱化了，建议增加秦艽“利小便”功效的研究。