痛泻要方防治肠易激综合征肝郁脾虚证的中枢调控机制

There is not much to do except relieving symptoms for the so called "syndromes" because even today we don't know those syndromes physiologically or pathologically. Neither do we have the bullet. While traditional Chinese medicine is capable of solving it which has been the bottle neck for conventional medicine based on its characteristics of "concept of holism" and "treatment based on syndrome differentiation". The previous branch program of 973 "Mechanism, Syndrome and Treating Law of Managing IBS Liver Aspect" showed that liver stagnation and spleen deficiency syndrome is the most common clinical syndrome type of IBS, and Tong Xie Yao Fang is a commonly used prescription for it through literature review, epidemiological investigation and blood biochemical examination. It further indicated that brain-gut peptide 5-HT of neuroendocrine network was also involved. Therefore we may study IBS, one of the "syndrome" diseases, to explore how Tong Xie Yao Fang regulates central nervous system to treat the "liver stagnation and spleen deficiency syndrome" type of IBS by understanding 5HT release and intake at the molecular, the genetic, the neural network levels and the overall level. We thus will provide the laboratory evidence for the prevention and treatment of the "syndrome" disease, and also offer the innovative attempt for TCM experimental research.

对于"综合征"疾病，由于现代医学缺乏确切的生理、病理学方面认识，且无特效的治疗手段，因此只能通过对症治疗而改善症状。以"辨证论治"、"整体观念"的特色的中医学，能够解决现代医学所面临的困境。在前期973计划子课题"肠易激综合征从肝论治的作用机制及证治规律"的研究中，文献梳理、临床流行病学调查和血液生化学检查的结果初步显示：肝郁脾虚证是IBS临床最为常见的证型，痛泻要方为治疗本病的常用方剂，且本病的发生与神经内分泌网络中的重要脑肠肽5-HT的代谢显著相关。因此，我们拟定以常见"综合征"类疾病- - "肠易激综合征"为研究对象，从5-HT释放及再摄取平衡入手，在分子水平、基因水平、神经网络水平以及整体水平，探讨痛泻要方防治肝郁脾虚型IBS的中枢调控机制。为"综合征"类疾病的防治提供实验室依据，也为中医理论思维指导现代科学实验研究提供创新性尝试。

肠易激综合征的临床表现主要以抑郁、焦虑和胃肠道等症状为主。5-HT在中枢水平的改变可导致失眠、焦虑等精神行为异常，在胃肠道水平的改变可导致腹痛、腹泻等异常。这与肝郁脾虚型肠易激综合征在临床上的表现相吻合，本课题即主要论证痛泻要方通过调节5-HT信号系统来防治IBS肝郁脾虚证这一科学假设。首先，运用“束缚应激+番泻叶灌胃法”构建IBS肝郁脾虚证动物模型；然后，用痛泻要方和匹维溴铵进行干预，并于实验结束后运用ELISA、PCR、免疫组化等方法检测组织中5-HT、5-HT前体合成物质（TPH）、5-HT重摄取物质（SERT）、VIP、和Cx43的表达。最后发现痛泻要方可降低血清、结肠、下丘脑中5-HT的含量；降低血清、结肠VIP的含量；降低海马、皮质、下丘脑中TPH的含量以及升高海马、皮质、下丘脑中SERT的含量；降低下丘脑中Cx43的平均光密度值来防治肠易激综合征。说明痛泻要方可以通过调节5-HT的释放和重摄取机制，使5-HT的含量恢复平衡来防治IBS肝郁脾虚证，同时也可以调控脑肠肽中VIP的含量以及缝隙链接蛋白Cx43的平均光密度值来达到防治IBS肝郁脾虚证的目的。