基于“辨体论治”思想研究调体方药过敏康通过肠肺共调节“菌群-PRRs-DCs”轴防治过敏性疾病的机制

本课题组在国内率先系统性开展过敏体质研究，前期以“辨体论治”为指导研制中药组方过敏康，临床干预过敏体质防治过敏性疾病收到了良好效果，实验发现该组方可明显改善树突状细胞（DCs）功能异常。本项目结合“共生菌群通过模式识别受体（PRRs）调控DCs分化”以及过敏性疾病“肠-肺”交叉对话的新进展，提出假说：通过肠肺共调节“菌群-PRRs-DCs”轴是过敏康调体防治过敏性疾病的重要机制。拟根据中医体质学“禀赋遗传论”，使罹患过敏性疾病的雌雄小鼠交配生育过敏体质子代，建立动物模型。再以过敏康干预，观察预防组、治疗组和对照组过敏反应评分、肠道、呼吸道菌群和PRRs、DCs指标，鉴定肠-肺共同关键菌。最后，给条件性无菌小鼠移植关键菌，验证过敏康通过肠-肺共调节菌群-PRRs-DCs防治过敏反应的效果和机制。本研究对深入阐释过敏体质生物学基础及调体防治过敏性疾病机制、推动“辨体论治”临床应用具有重要意义。

Our group is the first to systematically carry out allergic constitution research in China.With the guidance of " treatment based on constitution differentiation ", Guominkang, a Chinese herbal formula, has obtained a great effect on prevention and treatment of allergic diseases. It was found that Guominkang could remarkably improve the dysfunction of dendritic cells (DCs) in allergic constitution population. Allergic diseases have "intestinal-lung" cross-talk, and flora regulate the differentiation and maturation of DCs through pattern recognition receptors (PRRS). On the basis of the previous research, the hypothesis is put forward that co-regulation of " flora -PRRs-DCs" axis by intestine and lung is an important mechanism of Guominkang to prevent and treat allergic diseases. According to the "endowment inheritance theory" of TCM constitution, the female and male mice with allergic diseases will mate to produce allergic offspring and establish animal models. OVA will be used to stimulate allergic reaction, and Guominkang will be given to prevent and treat allergic reactions before and after stimulation. Western medicine and probiotics will be set up as control groups. Allergic symptom scores in each group will be observed. The structure and abundance of intestinal and respiratory tract flora, PRRs and the key cytokines of DCs differentiation in intestine, lung, spleen and blood will be detected. Then, the Key flora in gut and lung of mice with allergic constitution will be transplanted to the germ free mice induced by antibiotic.And the correlation among intestinal and pulmonary flora, PRRs and DCs will be analyzed. This study is of great significance to elucidate the biological basis of allergic constitution and the mechanism of constitution-modulating prescriptions in preventing and treating allergic diseases, and to promote the clinical application of " treatment based on constitution differentiation ".