基于脑-肠轴调控下丘脑OT神经元合成ITF探讨揉腹法促进胃黏膜损伤修复的作用机制

Gastric mucosa injury is the leading cause of gastric ulcer and acute or chronic gastritis in physiological and pathological process. This project has finished a preliminary clinical study which has demonstrated the efficacy of abdominal massage in the treatment of gastric mucosal lesions is effective, but its mechanism is still not clear. So this project uses abdominal kneading massage as the intervene measure, and put forward the hypothesis which is “Abdominal kneading Massage through the brain-gut axis neural pathways, and the abdominal visceral nerve plexus to transmit the information to the central nervous system, and thus stimulates the OT neurons in the hypothalamus, and increases the synthesis and secretion of ITF. thereby, it can promote the gastric epithelial cell proliferation, migration and closely connected, in order to achieve the role of gastric mucosal repairing”. This project plans to do the research on rats with gastric mucosal injury, and in order to verify the bridge function of brain-gut axis, we use the ELISA method to detect GAS and NPY content in hypothalamus and colon of rats; through fMRI exploratory to observe the target of abdominal massage in the central nervous system; using immunohistochemical method to observe the effect of abdominal massage on the activation of OT neurons. To detecting the abdominal massage whether enhancing the expression of hypothalamus, serum and gastric mucosa in ITF, we use RT-PCR and ELISA method. Based on the above experimental results, we want to reveal the mechanism how abdominal massage promoting gastric mucosa repairing. This project will further deepen the fundamental research of abdominal massage.

胃黏膜损伤是导致胃溃疡及急慢性胃炎发生的主要病理环节，本项目组前期临床研究已证实腹部推拿治疗胃黏膜损伤性疾病疗效确切，但其机制尚不明确。故本项目以临床有效手法“揉腹法”作为干预手段，提出“揉腹法借助脑-肠轴神经通路，通过腹部内脏神经丛将信息整合传导至中枢神经，进而激发下丘脑OT神经元，增加ITF的合成与分泌，从而促进胃黏膜上皮细胞的增殖、迁移与紧密连接，以达到修复胃黏膜的作用”的理论假说。拟以无水乙醇复制胃黏膜损伤大鼠模型，运用ELISA法检测大鼠下丘脑和结肠中GAS、NPY含量，以验证脑-肠轴的桥梁作用；通过fMRI探索性观察腹部推拿在中枢系统的作用靶点；应用免疫组化法观察腹部推拿对OT神经元的激活作用；采用RT-PCR和ELISA法检测腹部推拿是否提升了下丘脑、血清及胃黏膜中ITF的表达。综合以上实验结果以初步揭示腹部推拿促进胃黏膜修复的作用机制。本项目将进一步深化腹部推拿的基础研究。

胃黏膜损伤是导致胃溃疡及急慢性胃炎发生的主要病理环节，本项目组前期临床研究已证实腹部推拿治疗胃黏膜损伤性疾病疗效确切，但其机制尚不明确。故本项目以临床有效手法“揉腹法”作为干预手段，围绕假说展开研究，以清洁级SD大鼠进行胃黏膜损伤动物造模，首先从动物行为学上验证造模成功与否，并以旷场实验作为观察点，进一步观察了腹部推拿对于胃黏膜损伤大鼠症状及心理的影响；应用ELISA法检测腹部推拿干预前后，胃黏膜损伤大鼠模型结肠组织以及下丘脑中GAS、神经肽Y（NPY）等神经肽的含量变化，结果显示腹部推拿对胃黏膜损伤大鼠中枢和外周中GAS和NPY含量均有调节作用，验证了脑-肠轴在腹部推拿促进胃黏膜损伤修复起效过程中的桥梁作用；应用功能磁共振成像（fMRI）技术，探索性观察了腹部推拿在大脑中枢系统的效应靶点；应用免疫组化和Western Blot实验，检测下丘脑中c-fos蛋白的表达，结果显示腹部推拿能够显著下调c-fos蛋白的表达，验证了腹部推拿对下丘脑OT神经元具有激活作用；通过RT-PCR技术以及ELISA法等手段观察到腹部推拿能够显著上调下丘脑、血清中ITF的表达水平，验证了腹部推拿能够促进ITF在下丘脑和血清中表达。本研究初步揭示了揉腹法促进胃黏膜损伤修复的关键作用点和途径，对于深化腹部推拿的基础研究，及促进推拿学科的发展具有重要意义。