类风湿关节炎寒热方证对应的网络药理学研究策略

Research on network pharmacology of cold or heat herbal formula correspond with cold or heat syndromes of rheumatoid arthritis

类风湿关节炎是一种累及人体周围关节为主的多系统性、炎性自身免疫性疾病。乌头汤、黄连解毒汤分别对应治疗该病的寒证和热证,有效性已为一千多年临床实践所证实。寒热方证对应的复杂性、系统性和科学性,需要在分子网络药理学层次进一步探索和研究。研究策略如下:第一,通过基因芯片技术、代谢组学得到临床类风湿关节炎寒证、热证患者与健康人比较的差异基因和代谢物,构建和分析寒证和热证的分子网络。第二,根据乌头汤、黄连解毒汤的中药化学成分及其所作用的基因、蛋白质,构建分子药理网络。第三,通过分析寒热方证的分子药理网络,探索和发现两者关联的靶基因、靶蛋白,了解它们的功能、相互关系和作用。第四,构建布洛芬、美洛昔康、甲氨蝶呤、来氟米特及泼尼松的分子药理网络。第五,乌头汤、黄连解毒汤的分子药理网络分别与布洛芬、美洛昔康、甲氨蝶呤、来氟米特及泼尼松的分子药理网络相比较,探索和发现中药与西药分别作用于类风湿关节炎寒、热证的药理作用途径异同点。

Rheumatoid arthritis （RA） is a multi-system inflammatory and involving peripheral joints consisting mainly of autoimmune disease. Wutou decoction and Huanglian Jiedu decoction, corresponding to cold or heat syndromes of RA effectiveness has been confirmed by the two thousand years of clinical practice, and the complexity, systematisms and scientificalness of herbal formula corresponding to syndromes, need to be further explored at the molecular level and network pharmacology research. Firstly, compare the difference by gene chip technology and metabolomics get by clinical RA cold, heat syndrome patients and healthy human, import ingenuity pathway analysis （IPA） biological molecular analysis software, to construct and analyze the molecular network. Secondly, to find the chemical composition, the function of gene and protein of Wutou decoction and Huanglian Jiedu decoction, were imported into IPA software, to construct and analyze the molecular network. Thirdly, through analyzing the molecular network to explore and discover the relationship between target gene and protein, the understanding of their functions, relations and interactions. Fourthly, the molecular network of ibuprofen, meloxicam, methotrexate, leflunomide and prednisone was constructed and analyzed with IPA software. Fifthly, molecular pharmacology network of Wutou decoction and Huanglian Jiedu decoction were compared with ibuprofen, meloxicam, methotrexate, leflunomide and prednisone, it explored and discovered them respectively act on RA with cold or heat syndrome in the pharmacological mechanism of similarities and differences.