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在犬类去神经支配模型中,一氧化氮和非肾上腺素能、非胆碱能(NANC)神经的抑制作用得以保留:对小肠移植的启示。

Inhibition by nitric oxide and nonadrenergic, noncholinergic (NANC) nerves is preserved in a canine model of extrinsic denervation: implications for small bowel transplantation.

作者信息

Zyromski Nicholas J, Duenes Judith A, Sarr Michael G

机构信息

Gastroenterology Research Unit and Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Surgery. 2005 Nov;138(5):905-12. doi: 10.1016/j.surg.2005.06.029.

DOI:10.1016/j.surg.2005.06.029
PMID:16291392
Abstract

BACKGROUND

Small bowel transplantation (SBT) is complicated by changes in graft motility, especially in the early postoperative period. This dysmotility may be related in part to the extrinsic denervation necessitated by the procedure, but specific neurotransmitter response to SBT is incompletely understood. The aim of this study was to evaluate the role of nitric oxide and nonadrenergic, noncholinergic (NANC) enteric neural input in the nonimmunologic etiology of the dysmotility seen after SBT.

METHODS

A technique of jejunoileal extrinsic denervation (without disruption of mesenteric vascular supply) was used as a model of canine jejunoileal autotransplantation to avoid potential confounding factors such as ischemia-reperfusion and postallotransplant immunologic effects. Longitudinal smooth muscle strips from ileum and jejunum were studied with in vitro tissue chamber methodology at 0, 2, and 8 weeks after this experimental model to explore early and late effects of denervation. Effects of exogenous nitric oxide (NO) and electric field stimulation (EFS), which releases native, endogenous enteric neurotransmitters) were evaluated in neurally intact control dogs and those undergoing extrinsic denervation.

RESULTS

Exogenous NO caused a dose-dependent inhibition of spontaneous contractile activity and in some muscle strips a decrease in basal tone in both groups of dogs. These effects were unchanged by neural blockade with tetrodotoxin and preserved after extrinsic denervation. EFS produced inhibition of spontaneous contractile activity in ileum and a complex, inconsistent response in jejunum. The response to EFS in both ileum and jejunum was unchanged after extrinsic denervation.

CONCLUSIONS

Nitric oxide inhibits contractile activity in canine longitudinal muscle of small bowel. Motility changes seen after this large animal model of extrinsic denervation are not caused by changes in NO or NANC neural function. The variability observed between different segments of intestine is important to consider in the context of SBT.

摘要

背景

小肠移植(SBT)会因移植物运动的改变而变得复杂,尤其是在术后早期。这种运动障碍可能部分与手术所需的外在去神经支配有关,但对SBT的特定神经递质反应尚未完全了解。本研究的目的是评估一氧化氮和非肾上腺素能、非胆碱能(NANC)肠神经输入在SBT后出现的运动障碍的非免疫病因中的作用。

方法

采用空肠回肠外在去神经支配技术(不破坏肠系膜血管供应)作为犬空肠回肠自体移植模型,以避免潜在的混杂因素,如缺血再灌注和同种异体移植后的免疫效应。在该实验模型后的0、2和8周,采用体外组织室方法研究回肠和空肠的纵向平滑肌条,以探讨去神经支配的早期和晚期影响。在神经完整的对照犬和接受外在去神经支配的犬中评估外源性一氧化氮(NO)和电场刺激(EFS,释放天然内源性肠神经递质)的作用。

结果

外源性NO在两组犬中均引起剂量依赖性的自发收缩活动抑制,在一些肌条中基础张力降低。这些作用不受河豚毒素神经阻滞的影响,在外在去神经支配后仍得以保留。EFS抑制回肠的自发收缩活动,在空肠中产生复杂、不一致的反应。外在去神经支配后,回肠和空肠对EFS的反应均未改变。

结论

一氧化氮抑制犬小肠纵向肌的收缩活动。这种大型动物外在去神经支配模型后出现的运动变化不是由NO或NANC神经功能的改变引起的。在SBT的背景下,考虑不同肠段之间观察到的变异性很重要。

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引用本文的文献

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Effect of chronic, extrinsic denervation on functional NANC innervation with vasoactive intestinal polypeptide and substance P in longitudinal muscle of rat jejunum.慢性外源性去神经支配对大鼠空肠纵行肌中含血管活性肠肽和P物质的功能性非肾上腺素能非胆碱能神经支配的影响。
Neurogastroenterol Motil. 2008 Mar;20(3):243-52. doi: 10.1111/j.1365-2982.2007.01021.x. Epub 2007 Oct 17.
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Long-term effects of extrinsic denervation on VIP and substance P innervation in circular muscle of rat jejunum.外在去神经支配对大鼠空肠环行肌中血管活性肠肽和P物质神经支配的长期影响。
J Gastrointest Surg. 2007 Oct;11(10):1339-50. doi: 10.1007/s11605-007-0212-1. Epub 2007 Jul 17.