内脏高敏感是肠易激综合征（IBS）的主要病理生理特征之一，促肾上腺皮质激素释放因子（CRF）作为下丘脑-垂体-肾上腺轴参与应激反应的关键调节因子，中枢CRF通过激活其受体CRF1参与应激诱导的内脏高敏感。痛泻要方作为中医临床治疗肝郁脾虚型IBS的经典方剂具有明确缓痛功效，既往研究显示其可调节脑-肠轴中多种脑-肠肽的分泌，但其作用机制仍不明确。本项目从脑肠轴出发以CRF为切入点，围绕中枢CRF/CRF1参与肠易激综合征内脏高敏感发生这一科学认识，利用母子分离联合慢性束缚建立肝郁脾虚型IBS大鼠模型，以即早基因c-fos探索参与内脏高敏感的中枢区域并分析痛泻要方靶向部位，重点研究靶向组织CRF、CRF1、GRK3/6及β-arrestin1/2的表达变化，并检测AC、cAMP及PKA含量，基于CRF/CRF1系统阐明痛泻要方临床缓痛的中枢机制，为治疗IBS中药的作用机制研究提供思路。

Visceral hypersensitivity has been supposed to be one of the key pathophysiological characteristics in irritable bowel syndrome (IBS). Corticotropin releasing factor (CRF), one of the key hormones in hypothalamic-pituitary-adrenal axis (HPA)-mediated stress responses, is involved in stress-induced visceral hypersensitivity through central CRF/CRF1 pathway. Tongxie Yaofang decoction (TYD) as a classical prescription of traditional Chinese medicine is used for treating IBS with alleviating pain and anti-diarrheal effect. Previous studies showed that TYD regulates a variety of brain gut peptides secretion to maintaining the balance of brain-gut axis. However, its mechanism of action is still unclear. In view of a close relationship between central CRF/CRF1 and visceral hypersensitivity, the present study is designed to explore the mechanism of action of TYD in alleviating visceral hyperalgesia. Firstly, the effect of TYD on visceral hypersensitivity is evaluated in neonatal maternal separated male rats by colorectal distention. The c-fos and p-CREB expression in central tissue including brain and spine cord is tested to assure the central zone, of which takes part in the hyperalgesia. Meanwhile, the targeted tissue of TYD exerting lower visceral hypersensitivity is also explored. The expression of CRF/CRF1, GRK3/6 and β-arrestin1/2, and the level of AC, cAMP and PKA in targeted tissues are explored to demonstrate that TYD relieves visceral hypersensitivity of irritable bowel syndrome through central CRF/CRF1 signaling pathway. What is more, this project provides option for the research of traditional Chinese medicine on treating IBS.