基于孤束核及其CB1受体调节机制的电针干预TLESR研究

Transient lower esophageal sphincter relaxation (TLESR) is the main mechanism of gastric esophagitis reflux disease (GERD), in which nucleus of the solitary tract (NTS) and Cannabinoid type 1 (CB1) play important roles. Electroacupuncture on Zusanli (ST36) may active CB1 receptors in NTS, inhibit the pathway of cAMP/PKA, regulate the electro-activity of NTS, and then reduce TLESR. The rat model of gastric distension-induced TLESR will be used in this experiment. The Lower esophageal sphincter pressure (LESP), TLESR changes and TLESR combined gastricesophagitis reflux will be measured by the low compliance capillary perfusion manometry system, to observe the effect of electroacupuncture for GERD; The neuronal discharge of NTS, the protein expression of CB1 receptor, cAMP, and PKA will be detected to explore the mechanism; Also, the NTS will be destroyed in a separate EA group to partially disproof of the mechanism. This study will determine the central mechanism of TLESR, and apply a new mechanism of EA treatment for GERD.

一过性食管下括约肌松弛（transient lower esophageal sphincter relaxation, TLESR）是胃食管反流病（GERD）的主要机制。孤束核（NTS）及其大麻素1（Cannabinoid type 1，CB1）受体在TLESR的形成中扮演着重要角色。电针足三里可能通过激活NTS的 CB1受体，抑制cAMP/PKA通路，从而调节NTS的电活动，抑制或减少TLESR。本研究采用胃扩张诱发的TLESR模型，应用低顺应性毛细管灌注测压系统检测食管下括约肌压力、TLESR程度、以及TLESR合并反流发生次数以评价电针的干预效应；通过检测NTS神经元放电、以及CB1受体、cAMP、PKA在NTS的蛋白表达，研究电针的干预机制；同时通过损毁孤束核以部分反证其中枢机制。本研究将证实TLESR发生的中枢机制，并为电针干预GERD提供新的治疗机理。