Day-course changes in defecation refllex after rectal anastomosis and repairing the defecation reflex by promoting regeneration of the reflex pathways in the enteric nervous system by local treatment of BDNF

直肠吻合术后排便反射的日程变化以及BDNF局部治疗促进肠神经系统反射通路再生修复排便反射

基本信息

批准号：
18591477
负责人：
FUJII Hisao
金额：
$ 1.72万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591477/
关键词：
brain-derived neurotrophic factor centeric nervous system internal anal sphincter plasticity guinea pig

项目摘要

Moderate rectal distension elicits rectal (R-R) reflex contractions and simultaneous internal anal sphincter (R-IAS) reflex relaxations that together comprise the defecation reflex. Both reflexes are controlled by (1) pelvic nerves, (2) lumbar colonic nerves, and (3) enteric nervous system. The aim of the present study was to explore a novel approach to repairing the defecation reflex dysfunction using the plasticity of enteric nervous pathways. Experiments were performed in anesthetized guinea pigs with ethyl carbamate. The rectum 30 mm oral from anal verge was transected without damage to extrinsic nerves, and subsequent end-to-end one layer anastomosis was performed. Recovery of the defecation reflex and associated reflex pathways were evaluated. Eight weeks after sectioning of intrinsic reflex nerve pathways in the rectum, the defecation reflex recovered to the control level, accompanied with regeneration of reflex pathways. The 5-HT_4 receptor agonist, mosapride (0.5 and 1.0 mg/kg) significantly (P < 0.01) enhanced the recovered defecation reflex eight weeks after surgery. Two weeks after the local treatment with brain-derived neurotrophic factor (BDNF: 10^-6g/ml)at the rectal anastomotic site, the R-IAS reflex relaxations recovered and some bundles of fine nerve fibers were shown to interconnect the oral and anal ends of the myenteric plexus. These results suggested a possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system with local application of BDNF.

中度直肠扩张引起直肠（R-R）反射性收缩和同时肛门内括约肌（R-IAS）反射性松弛，共同构成排便反射。两种反射均由 (1) 骨盆神经、(2) 腰结肠神经和 (3) 肠神经系统控制。本研究的目的是探索一种利用肠神经通路的可塑性修复排便反射功能障碍的新方法。实验在用氨基甲酸乙酯麻醉的豚鼠中进行。在不损伤外在神经的情况下，从肛缘口口30mm处横断直肠，随后进行端到端一层吻合。评估排便反射和相关反射途径的恢复。直肠内反射神经通路切断后八周，排便反射恢复至控制水平，同时反射通路再生。 5-HT_4受体激动剂莫沙必利（0.5和1.0 mg/kg）显着（P < 0.01）增强术后八周恢复的排便反射。直肠吻合口局部脑源性神经营养因子（BDNF：10^-6g/ml）治疗两周后，R-IAS反射松弛恢复，部分细神经纤维束连接口腔和肛门肌间神经丛的末端。这些结果表明，局部应用 BDNF 可以通过促进肠神经系统反射通路的再生来修复肛门功能障碍。