A new possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system

A new possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system
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DOI:
10.1152/ajpgi.00345.2007
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发表时间:
2008-04-01
影响因子:
4.5
通讯作者:
Takaki, Miyako
Takaki, Miyako
中科院分区:
医学2区
文献类型:
--
作者:
Katsui, Renta;Kojima, Yu;Takaki, Miyako

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适度的直肠膨胀引起直肠-直肠反射收缩,同时引起直肠-内肛门括约肌反射松弛,共同构成排便反射。这两种反射都是由1)骨盆神经、2)腰结肠神经和3)肠神经系统控制的。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。在未损伤外源性神经的情况下,切除距肛缘30 mm的直肠,行端到端单层吻合。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- ht4受体激动剂莫沙必利(0.5和1.0 mg/kg)显著(P < 0.01)增强术后8周的排便反射恢复。在直肠吻合口局部应用脑源性神经营养因子(BDNF: 10(-6) g/ml)治疗2周后,直肠-内肛门括约肌反射恢复松弛,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 recto-rectal reflex contractions and simultaneous recto-internal anal sphincter 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 by using the plasticity of enteric nervous pathways. Experiments were performed in anesthetized guinea pigs with ethyl carbamate. The rectum 30 mm oral from the 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-HT4-receptor agonist mosapride (0.5 and 1.0 mg/kg) significantly (P < 0.01) enhanced the recovered defecation reflex 8 wk after surgery. Two weeks after local treatment with brain-derived neurotrophic factor (BDNF: 10(-6) g/ml) at the rectal anastomotic site, the recto-internal anal sphincter 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.