肠易激综合症（IBS）的发生与神经或精神因素导致的内脏敏感性异常密切相关，中枢下丘脑室旁核（PVN）区和蓝斑（LC）区CRH系统和NE系统的异常激活可导致内脏敏感性改变，但其分子机制还尚不清楚。我们前期工作发现，中枢CRHR1的高表达与子代类焦虑样行为和内脏高敏感有关。本项目利用侧脑室注射CRHR1小干扰RNA和内脏敏感性检测，明确中枢CRHR1在母婴分离诱发子代IBS发生中的关键“驱动”作用；同时利用分子生物学和细胞生物学手段，检测CRHR1介导的中枢PVN区和LC区CRH系统和NE系统的激活情况；研究Crhr1基因启动子区关键CG位点的甲基化修饰水平和组蛋白甲基化修饰情况；阐明Crhr1基因的表观遗传学调控机制在IBS发生中的作用。拟通过本研究，为临床上由于精神心理因素导致的IBS易感性增加提供一定的理论基础，为探索IBS治疗方法提供新的靶点。

Psychological factors are known to be key components in the outcome of clinical manifestations of irritable bowel syndrome (IBS). The dysregulation of CRH system and NE system in paraventricular nucleus (PVN) and locus nucleus (LC) is associated with the abnormal gastrointestinal motility, but the molecular mechanisms have not yet been elucidated. We previously found that the activation of CRH receptor 1 (CRHR1) tightly linked to the change of anxiety-like behavior and visceral sensitivity in rats. In this study, we firstly examined the change of visceral sensitivity with administration of CRHR1 siRNA in lateral ventricle to identify whether central CRHR1 was a key regulator in IBS symptoms induced by maternal separation. Secondly, we detected the CRHR1-related activation of CRH system and NE system in PVN and LC. Thirdly, we investigated whether the CRHR1 upregulation was modulated by the DNA methylation and histone methylation, in order to illuminate the epigenetic mechanism of Crhr1 gene expression in the pathogenesis of IBS. Targeting these mechanisms may open new target therapeutic venues in the treatment of IBS symptoms induced by psychological factors.