Kasparek M S, Fatima J, Iqbal C W, Sarr M G
Department of Surgery and Gastroenterology Research Unit (GU 10-01), Mayo Clinic, Rochester, MN 55905, USA.
Neurogastroenterol Motil. 2008 Jul;20(7):808-17. doi: 10.1111/j.1365-2982.2008.01083.x. Epub 2008 Feb 11.
Extrinsic denervation contributes to enteric motor dysfunction after small bowel transplantation (SBT). Our aim was to determine changes in nonadrenergic, noncholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P (Sub P) in rat jejunal circular muscle after SBT. Muscle strips were studied in tissue chambers from six groups of rats (n > or = 6 per group): naïve controls (NC), animals 1 week after anaesthesia/sham celiotomy (SC-1), and 1 and 8 weeks after jejunal and ileal transection/reanastomosis (TA-1, TA-8) and after syngeneic, orthotopic SBT (SBT-1, SBT-8). Response to exogenous VIP and Sub P and their endogenous release during electrical field stimulation (EFS) were studied. Exogenous VIP and Sub P caused a dose-dependent inhibition and stimulation of mechanical activity in all groups respectively (P < 0.05). The responses to VIP and Sub P were decreased (compared to NC) in all groups at 1 and 8 weeks postoperatively. The VIP antagonist ([D-p-Cl-Phe(6),Leu(17)]-VIP) did not prevent the inhibition by exogenous VIP in any group, while the Sub P antagonist ([D-Pro(2),D-Trp(7,9)]-Sub P) prevented the effect of exogenous Sub P in NC, TA-8 and SBT-8 (P < 0.05). Responses to exogenous VIP were unaffected by the nitric oxide synthase inhibitor l-N(G)-nitro arginine and precontraction of muscle strips with Sub P. Endogenous release of VIP and Sub P during EFS was preserved after SBT. In circular muscle of rat jejunum, changes in neuromuscular transmission with VIP and Sub P during the first 8 weeks after SBT are not mediated by extrinsic denervation.
外在去神经支配会导致小肠移植（SBT）后肠道运动功能障碍。我们的目的是确定SBT后大鼠空肠环行肌中含血管活性肠肽（VIP）和P物质（Sub P）的非肾上腺素能、非胆碱能神经支配的变化。对六组大鼠（每组n≥6）的肌条在组织浴槽中进行研究：未处理的对照大鼠（NC）、麻醉/假剖腹术后1周的动物（SC-1），以及空肠和回肠横断/再吻合术后1周和8周的动物（TA-1、TA-8），还有同基因原位SBT术后1周和8周的动物（SBT-1、SBT-8）。研究了对外源VIP和Sub P的反应以及电场刺激（EFS）期间它们的内源性释放。外源VIP和Sub P分别在所有组中引起剂量依赖性的机械活动抑制和刺激（P<0.05）。术后1周和8周时，所有组对VIP和Sub P的反应均降低（与NC组相比）。VIP拮抗剂（[D-p-Cl-Phe(6),Leu(17)]-VIP）在任何组中均未阻止外源VIP的抑制作用，而Sub P拮抗剂（[D-Pro(2),D-Trp(7,9)]-Sub P）在NC组、TA-8组和SBT-8组中阻止了外源Sub P的作用（P<0.05）。对外源VIP的反应不受一氧化氮合酶抑制剂L-N(G)-硝基精氨酸以及用Sub P预收缩肌条的影响。SBT后EFS期间VIP和Sub P的内源性释放得以保留。在大鼠空肠环行肌中，SBT后前8周内VIP和Sub P介导的神经肌肉传递变化并非由外在去神经支配介导。
