基于津液理论探讨肠道菌群调控AQP3/MUC2介导STC发病机制研究

慢传输型便秘（STC）是临床常见病、多发病，与心脑血管意外等疾病密切相关，严重威胁人类身心健康。目前治疗效果不佳且检查治疗花费巨大，主要在于其发病机制尚不明确。研究发现肠道菌群与便秘关系密切，但是具体机制研究较少。课题组前期发现STC发病中存在津液异常且与水通道蛋白3(AQP3)和黏蛋白2（MUC2）异常表达相关，因此我们提出肠道菌群可能通过调控AQP3和MUC2介导STC发生。本课题拟在中医津液理论的指导下，从“津”“液”出发，结合肠道菌群及其代谢产物，以AQP3/MUC2介导结肠水/黏液代谢为切入点，利用便秘模型大鼠，抗生素耗竭，菌群移植及测序等手段，探讨肠道菌群和结肠“津”“液”在STC发生中的相关性和因果性；通过细胞实验和药物干预，深入阐释肠道微生态系统异常导致便秘的分子生物学机制。从津液角度探讨肠道菌群在STC发生中的机制，扩大津液理论现代内涵，也为中医药防治STC提供新思路。

Slow transit constipation (STC) is a common and frequently occurring disease in the clinic, and it is a severe threat to human physical and mental health. However, the effectiveness of treatment on Constipation is poor, and consumes a lot of healthcare resources, mainly because its pathogenesis is unknown. In recent years, it has been found that there is a close relationship between intestinal microbiota and constipation. Intestinal microbiota related therapy shows great potential in the prevention and treatment of constipation, but the specific mechanism is less studied. In the previous study, our research group has found that there was a disturbance of water metabolism in STC, which was related to the abnormal expression of AQP3 and MUC2. Therefore, we suggest that intestinal microbiota may mediate STC by regulating AQP3 and MUC2. To verify the hypothesis, with the guidance of body fluid theory of traditional Chinese medicine, starting from "thin fluid" and "thick fluid", combined with intestinal and its metabolites, taking colon water/mucus metabolisms mediated by AQP3/MUC2 as the cut-in point, our team will use constipation model rats, antibiotic depletion, fecal microbiota transplantation, sequence and other means to explore the correlation and causality between intestinal microbiota and "thin fluid" and "thick fluid" in chronic constipation. Through cell experiment and drug intervention, the molecular biological mechanism of constipation caused by intestinal microbiota abnormality will be expounded. In this study, the mechanism of intestinal microbiota in the occurrence of constipation will be discussed from the perspective of body fluid and the modern connotation of body fluid theory will be expanded, We also provide new ideas about the prevention and treatment of STC by traditional Chinese medicine.