基于脑肠互动的标识脑肠肽与戊己丸作用机理相关性研究

Brain-gut peptides (BGP) are physiological active substances, located in both brain and gastrointestinal tract. Excitatory and inhibitory transmission maintain a functional balance in normal conditions. But this harmonious state was broken by pathologic conditions, such as irritable bowel syndrome (IBS). In the light of consensus which brain-gut interaction plays a critical role in the occurrence of IBS, BGP are investigated as breakthrough point, using multiple techniques, such as microdialysis, molecular biology and instrumental analysis, considering multistrata perspectives, such as function, secretion of transmitter, action on cell and pharmacokinetics. The visceral hyperalgesia, colonic motility and brain-gut peptide markers, vanillin receptor subtype 1, and the concentration-time-effect of Wujiwan active ingredients are explorated to certify the significance of brain-gut Interaction in the occurrence and treatment of IBS, and to study the mechanism of Wujiwan.

脑肠肽(BGP)是一类同时存在于脑和肠道的有生理活性的物质。正常情况下，体内多种兴奋性及抑制性BGP保持平衡，但在肠易激综合征(IBS)等疾病状态失衡。本项目基于对IBS发病过程中脑与肠相互影响的认识；以BGP为切入点；综合运用微透析、分子生物学、现代分析等技术和方法，从功能、递质、细胞、药物动力学等角度；围绕内脏痛觉敏感、结肠动力与标识脑肠肽、辣椒素受体，以及戊己丸活性成分在脑和血液中的“药-时-效”关系；进一步证实脑肠互动在IBS发病、治疗中的重要意义，探讨戊己丸治疗IBS的作用机理。

脑肠肽(BGP)是一类同时存在于脑和肠道的有生理活性的物质。正常情况下，体内多种兴奋性及抑制性BGP保持平衡。本项目研究发现在乙酸灌肠加束缚应激法建立IBS模型大鼠的结肠、脑组织和血浆内的降钙素基因相关肽、胃动素（MTL）、神经肽Y、P物质、5-羟色胺等十余种脑肠肽的浓度与正常动物有显著变化。我们通过综合运用微透析、分子生物学、现代分析等技术和方法，研究了BGP在脑和结肠局部的作用和戊己丸活性成分在脑和血液中的“药-时-效”关系，计算得到各活性成分与标志性脑肠肽的相关性；并选择了相关性最大的两种成分进行验证，证实了戊己丸中活性成分吴茱萸碱对IBS的外周症状发挥了主要的作用。