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

适度的直肠膨胀引起直肠（R-R）反射收缩和同时的肛门内括约肌（R-IAS）反射松弛，它们共同构成排便反射。这两种反射都由(1)盆腔神经、(2)腰结肠神经和(3)肠神经系统控制。本研究旨在探讨利用肠道神经通路的可塑性修复排便反射功能障碍的新方法。实验用氨基甲酸乙酯麻醉豚鼠。在不损伤外源性神经的情况下，切除距肛缘30 mm的直肠，行端到端一层吻合。评估排便反射和相关反射通路的恢复情况。切除直肠内反射神经通路8周后，大便反射恢复到对照水平，并伴有反射神经通路的再生。5-HT_4受体激动剂莫沙必利（0.5、1.0 mg/kg）能显著增强术后8周的排便反射恢复（P < 0.01）。在直肠吻合口局部应用脑源性神经营养因子（BDNF: 10^-6g/ml）治疗2周后，R-IAS反射恢复松弛，肌肠丛口端和肛门端可见成束细神经纤维相互连接。提示局部应用BDNF可促进肠神经系统反射通路的再生，从而修复肛门功能障碍。

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.