基于肠道菌群经ROS/HIF-1α途径对肠巨噬细胞极化的调控研究“脾应长夏”的生物学机制

“脾应长夏”是中医原创经典理论“五脏应时”的重要思想，目前研究多局限于文献理论探讨，尚未见到结合季节节律探索中医脾生理功能的研究。前期研究发现，反映脾功能的肠道巨噬细胞在长夏湿热环境中更倾向于极化为M1型，且M1/M2极化平衡与肠道菌群的季节性调控相关，据此提出研究假说：“脾应长夏”的机制是：湿热环境中肠道菌群的适应性改变能够经ROS/HIF-1α途径实现对肠巨噬细胞M1/M2极化平衡的调控，从而维持肠道免疫稳态，促使机体适应长夏季节。本项目拟从肠道菌群和巨噬细胞极化的季节特征着手，联合菌群测序和代谢组学分析技术，通过五季生理模型和伪无菌鼠模型，以及长夏环境中的脾虚证模型，分别从生理探索和病理反证角度，系统研究“脾应长夏”的生物学机制。本研究不仅可以深化中医“脾应长夏”的科学内涵，为防治脾虚相关季节性疾病提供实验依据，为临床择时用药提供新的启示，还可以丰富肠道菌群及肠道免疫的时间节律研究。

"Spleen corresponds to late summer" is an important idea of​the theory of "Five Zang Organs correspding to the seasons", which are the original classic theories of traditional Chinese medicine. At present, most studies are limited to literature theory, and no studies have been conducted to explore the physiological function of spleen in TCM combining with seasonal rhythm. Previous studies have found that the gut macrophages tend to polarize as M1 in late summer when the environment is often hot and humid. And M1/M2 polarization balance is related to the seasonal regulation of intestinal flora. Accordingly we put forward research hypothesis: the mechanism of "spleen corresponds to late summer" is: Seasonal adaptive changes of intestinal flora can regulate the M1/M2 polarization balance of intestinal macrophages through the ROS/HIF-1α pathway. Such can maintain intestinal immune homeostasis, promote the body to adapt to late summer hot and humid environment. This project will study the seasonal characteristics of intestinal flora and macrophage polarization. In this study, the biological mechanism of "spleen corresponds to late summer" will be systematically studied from the physiological and pathological aspects respectively by using the five-season physiological model, the pseudo-sterile mouse model and the spleen deficiency syndrome model in late summer environment, combined with the microflora sequencing and metabonomics analysis technology. This study can not only deepen the scientific connotation of "spleen corresponds to late summer", provide experimental basis for the prevention and treatment of seasonal diseases related to spleen deficiency, provide new inspiration for clinical timing medication, but also enrich the research on the time rhythm of intestinal flora and intestinal immunity.