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大鼠小肠移植后回肠环形平滑肌的肾上腺素能去神经超敏反应

Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.

作者信息

Shibata C, Balsiger B M, Anding W J, Sarr M G

机构信息

Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota, UK.

出版信息

Dig Dis Sci. 1997 Nov;42(11):2213-21. doi: 10.1023/a:1018850214119.

DOI:10.1023/a:1018850214119
PMID:9398797
Abstract

Effects of small bowel transplantation (SBT) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SBT in rats. Orthotopic SBT was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/ reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.

摘要

小肠移植(SBT)对回肠运动的影响尚不清楚。本研究旨在探讨大鼠SBT后回肠环行肌自发收缩活动以及对胆碱能和肾上腺素能药物敏感性的变化。在同基因大鼠中进行原位SBT以避免免疫现象。取SBT后1周(n = 10)和8周(n = 10)大鼠的远端回肠环行肌条,拉伸至最佳长度(Lo),并测量Lo时的基础自发活动。在存在河豚毒素(TTX,10⁻⁶ M)的情况下,对胆碱能激动剂氨甲酰甲胆碱(Be,10⁻⁸ - 10⁻⁴ M)进行剂量反应实验,对肾上腺素能激动剂去甲肾上腺素(NE,10⁻⁸ - 10⁻⁴ M)进行有无TTX存在下的剂量反应实验。计算半数有效剂量(ED50,诱导50%效应的药物浓度的负对数)。我们还研究了选择性空肠回肠缺血/再灌注、肠切断/再吻合、未处理对照以及假手术对照的大鼠(每组n≥8)。各组基础自发活动无差异。与对照组织相比,SBT后大鼠或其他组对Be的敏感性无差异。SBT后,无论有无TTX存在,在SBT后1周和8周时对NE的超敏反应表现为ED50显著增加(分别为5.1±0.3对6.2±0.4和6.2±0.2;P<0.05)。在缺血再灌注、肠切断再吻合或假手术后未观察到超敏反应。结论是,回肠对NE的超敏反应与移植手术所致的外在去神经支配有关,可能是通过平滑肌而非肠神经上受体数量的增加介导的。

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Role of selective alpha and beta adrenergic receptor mechanisms in rat jejunal longitudinal muscle contractility.选择性α和β肾上腺素能受体机制在大鼠空肠纵行肌收缩性中的作用。
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