基于“大肠主津”探讨结肠AQP3/AQP9在STC发病中的作用机制研究

慢传输型便秘（STC）是肛肠、消化科的常见疾病，以老人和妇女多见，已对我国居民健康构成潜在威胁，其发病机制尚不明，笔者认为总与粪便含水量有关。研究表明水通道蛋白（AQPs）的功能及其调节机制与机体水液代谢密切相关，而AQP3/AQP9介导结肠吸收及分泌水分的作用逐渐得到认可。前期研究发现通便中成药调控AQP3表达，抑制结肠吸收水分而产生通便效应。为进一步探讨STC发病机制，本项目拟在“大肠主津”理论指导下，复制“津亏”便秘动物模型，检测造模后AQP3/AQP9功能和表达的变化，以及肠神经递质等调节因素的活性水平，并观察“增液行舟”法的干预作用，通过其“剂量-效应”、“时间-效应”关系，“以方测证”，证实AQP3/AQP9介导的结肠水代谢紊乱及调控失效是STC发病的重要环节之一，以期发现STC发病新理论、治疗新靶点，为通便药研发提供参考，同时为研究中药的通便机制提供依据。

Slow transit constipation(STC) is a common disease in department of colorectal surgery and gastroenterology,which tends to be prevalent in elders and women,posing a potential threat to health of Chinese residents. However,the mechanism of STC remains unclear, which tends to be related with fecal water content. Accumulating evidences demonstrate that aquaporins（AQPs） as well as its regulation may play a vital role in fluid homeostasis. More importantly,it has been gradually elucidated regarding water transfer in the colon mediated by AQP3/AQP9. Our previous study suggested that cathartic Chinese patent medicine may modulate the expression of AQP3 in the colon,which inhibits colonic water absorption leads to a laxative effect. The purpose of this project is to explore the pathogenesis of STC. Therefore, under the guidance of theory“large intestine governs fluid” in Traditional Chinese Medicine. Our group intends to mimic “fluid deficiency” syndrome in constipated rats,so as to observe the changes in the function and expression of AQP3/AQP9 as well as the level of neurotransmitters and other factors in the colon. After that,to examine the intervention by Zengyetang“increase water to facilitate the vehicle” in rats model. By discussing the “dose-effect” and “time-effect”, “using formula to verify syndrome”,it is expected to validate the abnormal colonic water metabolism mediated by AQP3/AQP9 as well as the disorder of its regulation in the pathogenesis of STC. Overall,it is expected to discover novel theory in the pathogenesis of STC and potential therapeutic target in treatment of STC by means of this project. Moreover,it may also serve as references for new drug development and pharmacology,and provide evidences for understanding the mechanism of Zengyetang in treating constipation.