基于脑肠轴对肝郁脾虚型肠易激综合症（IBS）肠道微生态及水液代谢组学的研究

Irritable bowel syndrome (IBS) is a typical psychosomatic which is closely related to psychology, physiology and pathology. Liver stagnation and spleen deficiency syndrome is most common in TCM clinical practise. Shugan Jianpi therapy possesses the properties of "reactive multi-component, multi-target effects and multi-pathways". Intestinal micro ecology and fluid metabonomics with characteristics of overall and dynamic core thinking are coincide with "system", "unity", "dialectics" theories of Traditional Chinese Medicine (TCM)，and it is a new idea to use intestinal micro ecology and water liquid metabonomics methods to study IBS and discuss the nature and mechanism of Chinese herb intervention. Using two-dimensional gel electrophoresis, biological mass spectrometry technology and other related technology, the project will detect brain-gut peptides along the axis of the hypothalamus, spinal cord, stomach and intestine in rats with IBS of liver stagnation and spleen deficiency syndrome，analyse their intestinal micro ecology and water liquid metabonomics，study the correlation between brain-gut peptide change and intestinal micro ecology, intestinal liquid water metabolism, and look for effective targets and pathways of TCM to treatment IBS in order to improve the level of IBS diagnosis and treatment and promote the modernization of Chinese medicine.

肠易激综合征(IBS)是一类心理、生理、病理相互作用形成的典型心身疾病，中医临床以肝郁脾虚证最为多见，使用疏肝健脾法治疗具有 “活性多组分、作用多靶点多途径”的特点。肠道微生态及水液代谢组学的“整体性、动态性”的核心思维与中医学“整体观、辨证观”理论体系相吻合，应用肠道微生态及水液代谢组学对IBS中医证的本质及中药复方作用机制是一个新的思路。本项目以脑肠轴为切入点，通过双向凝胶电泳和生物质谱等技术对肝郁脾虚证IBS大鼠下丘脑、脊髓、胃和肠这条轴线脑肠肽分析；并通过对肝郁脾虚型IBS模型大鼠肠道微生态及水液代谢组学进行系统性研究；探寻脑肠轴与肠道微生态、肠道水液代谢及中医证候学之间的相关性，进一步阐明IBS的发病机制，寻找中医复方制剂的有效靶点与途径，以期能够提高本病的诊治水平，促进中医药的现代化发展。

肠易激综合征（IBS）作为消化系统常见病，7%～21%的人群受其影响，其中腹泻型肠易激综合征（IBS-D）占1/3，严重影响了患者生活质量。现代医学认为IBS-D发病由多因素、多途径、多机制共同导致，但发病机制尚未明确。IBS是归属于“腹痛、腹泻、郁证”等的范畴，肝郁脾虚型是最为常见的证型，中医认为肝郁脾虚型IBS-D主要是由于情志失调，饮食不节以及外邪侵袭等因素共同形成，脾失健运，肝失疏泄，二者共为相因而发为此病。课题组前期临床观察发现院内制剂平胃胶囊在治疗IBS-D方面疗效显著，但其发挥效应属“多因微效”，是多个弱效应的整合作用，而其具体治疗的分子机制尚未阐明。目前认为，IBS的发病是由多因素复合作用共同形成，不能用单一的效应机制解释，脑肠轴的异常是IBS发病机制的重要机制。因此，本课题以脑肠轴为切入点，结合水液代谢及肠道菌群的变化影响，以肝郁脾虚型IBS-D大鼠为研究对象，观察各组大鼠体重变化、饮食饮水量、病理形态学改变、胃肠电活动及胃排空和肠推进，焦虑、抑郁样行为改变，借助ELISA、免疫组化、qRT-PCR、Western-Blot等方法，观察平胃胶囊对各组大鼠脑肠肽水平表达的影响以及对肠道水液代谢、肠道菌群的影响，结果发现平胃胶囊可纠正不同脑肠肽水平的分泌和表达；也可调节肠道通透性即肠道菌群的改变来发挥作用。故认为通过脑肠轴纠正异常脑肠肽水平的表达和分泌可能是平胃胶囊治疗肝郁脾虚型IBS-D的机制与作用途径，同时也可能通过调节肠道水液代谢水平及肠道菌群的变化来起到治疗作用。