【摘要】 背景:胃起搏治疗胃动力障碍性疾病已引起广泛关注,但其作用机制尚不清楚。目的:观察不同5-羟色胺(5-HT)受体拮抗剂对胃慢波和控制胃慢波所需的刺激能量的影响,探讨胃起搏的作用机制。方法:通过手术建立Wistar大鼠胃起搏模型,并将其分成8组(每组8只),分别经腹腔给予不同浓度的美西麦角(5-HT1、5-HT2受体非选择性拮抗剂)、托烷司琼(5-HT3受体拮抗剂)和GR113808(5-HT4受体拮抗剂),以0.9%NaCl溶液作为对照。以多导生理信号分析系统记录胃慢波,以频谱分析法分析不同5-HT受体拮抗剂对胃慢波的影响。结果:与对照组相比,美西麦角和托烷司琼对胃慢波均无影响。GR113808能引起胃电紊乱,大剂量(2.5×10-4mol/L)时能使大鼠正常慢波百分比较对照组显著降低(P<0.01);而胃起搏能纠正GR113808引起的胃电紊乱,使正常胃慢波百分比得到改善(93.9%±1.9%),控制胃慢波所需的刺激能量较对照组显著降低(P<0.01)。大剂量GR113808诱发的胃电节律异常以胃电过缓为主(42.3%±3.4%)。中、小剂量GR113808(2.5×10-5mol/L和2.5×10-6mol/L)对大鼠正常胃慢波百分比影响不明显,与对照组相比无显著差异;中等剂量组控制胃慢波所需的刺激能量较对照组显著降低(P<0.05),小剂量组则无显著差异。结论:5-HT4受体拮抗剂GR113808能引起胃电紊乱,而胃起搏以较小的刺激能量就能纠正之,提示胃起搏可能(至少部分)是通过5-HT4受体的介导而对胃慢波进行调控的。更多还原

【Abstract】 Background:Gastric pacing as a therapeutic modality for gastric dysmotility has received much attention,however,its mechanism remains uncertain.Aims:To observe the effect of antagonists of various 5-hydroxytryptamine(5-HT)receptors on gastric slow waves and energy of pacing stimuli needed to entrain gastric slow waves,and hence to investigate the mechanisms of gastric pacing in rats.Methods:The Wistar rat models of gastric pacing with two pairs of electrodes were constructed,and were divided into eight groups(each eight rats),methysergide(nonselective antagonist of 5-HT1 and 5-HT2 receptor),tropisetron(antagonist of 5-HT3 receptor)and GR113808(antagonist of 5-HT4 receptor)in various doses were respectively administrated intraperitoneally(ip),saline(ip)was used as control.Gastric slow waves were recorded by multi-channel physiological signal analytical system.Effects of antagonists of various 5-HT receptors on gastric slow waves were analyzed by spectral analysis.Results:Compared with the control,methysergide and tropisetron,these medications did not alter gastric slow waves,but GR113808 induced gastric dysrhythmia.Percentage of normal slow wave in large dose GR113808(2.5×10-4 mol/L)-treated groups was significantly decreased than that of the controls(P<0.01).Gastric pacing could normalize gastric dysrhythmia induced by GR113808,and percentage of normal slow wave was ameliorated(93.9%±1.9%),and energy of pacing stimuli needed to entrain gastric slow waves was markedly decreased than that of the controls(P<0.01).The main dysrhythmia during injection of large dose GR113808 was bradygastria(42.3%±3.4%).However,percentage of normal slow wave in moderate and small doses of GR113808(2.5×10-5 mol/L,2.5×10-6 mol/L)-treated groups were not different from that of the controls.Energy of pacing stimuli needed to entrain gastric slow waves in small dose GR113808 was not different from that of the controls whereas energy of pacing stimuli needed in moderate dose GR113808 was lower than that of the controls(P<0.05).Conclusions:Antagonist of 5-HT4 receptor GR113808 could induce gastric dysrhythmias,gastric pacing can entrain the gastric slow waves with small energy of pacing stimuli,suggesting that the gastric pacing-induced entrainment effect on gastric slow waves is mediated,at least in part,via the 5-HT4 subtype receptor.更多还原