慢性内脏高敏性大鼠结肠内P物质及其NK1受体表达的改变

目的　研究慢性应激刺激所致内脏高敏性大鼠和正常大鼠结肠内P物质 (substanup)及其NK1受体表达的改变 ,探讨内脏高敏感性产生的可能机制。方法　 40只新生SD大鼠 ,随机分为 2组 :慢性应激模型组、正常对照组 ,每组 2 0只。模型组大鼠在出生后第 8天到 2 1天 ,每天接受结直肠扩张刺激 ;分别在第 8周、12周观察大鼠的腹部回缩反射 (AWR)和玻璃小球排出情况 ,进行肠道敏感性评估 :采用RT PCR方法检测二组大鼠结肠组织内P物质及其NK1受体mRNA的表达 ,并运用免疫组化SABC法观察NK1受体的分布。结果　模型组较正常对照组大鼠腹部收缩阈值明显降低 (P <0 .0 1) ,玻璃小球排出时间缩短 (P <0 .0 1) ;P物质及其NKl受体mRNA的表达明显增加 (P <0 .0 1) ,NK1受体免疫反应阳性产物显著浓密 ,以平滑肌层和黏膜层为著。结论　SP及其NK1受体表达增加在大鼠肠道高敏感性、动力紊乱的产生机制中可能起重要作用

Increased expression of SP and NK1 receptor in rat colon of chronic visceral hypersensitivity

Objective To investigate the changes of expression of Substance P (SP) and NK1 receptor in rat colon of chronic visceral hypersensitivity and discuss the possible mechanism of visceral hypersensitivity associated with IBS. Methods Fourty SD rats were randomly divided into two groups:chronic irritation models and controls. The model was established by colorectal distention daily in the neonatal rats between postnatal 8 and 21 days. The threshold of abdominal withdrawal reflex(AWR) during rectal distension and the time of glass pellets output was evaluated at postnatal 8 and 12 weeks respectively, the expression of SP and NK1 receptor mRNA in the colon was studied by RT PCR, and the distribution of NK1 receptors were identified by immunohistochemistry (IHC) in the colon wall of rats. Results In contrast to the controls, chronic irritation models showed decrease in the threshold of AWR and time of glass pellets output; the levels of SP and NK1 receptors mRNA was significantly increased; simultaneously, the NK1 immunoreaction positive products were densely distributed in the smooth muscle layer and epithelium of colon wall of chronic irritation models. Conclusion Increased expression of SP and NK1 receptor might play an important role in the pathogenesis of visceral hypersensitivity associated with IBS in the chronic irritation models.