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目的:探讨并比较Ghrelin及其拟似剂生长激素释放肽-6(GHRP-6)对豚鼠胃平滑肌舒缩活动的影响及机制。方法:采用电场刺激豚鼠胃底和胃窦部肌间神经方法,观察Ghrelin和GHRP-6对胃平滑肌舒缩活动的影响,并通过观察一氧化氮合酶(NOS)抑制剂Nω-硝基-L-精氨酸(L-NNA)、一氧化氮前体L-精氨酸(L-AA)对Ghrelin和GHRP-6调控胃平滑肌运动的影响以阐明其机制。结果:不同频率(1~16Hz)电刺激胃底部肌间神经,平滑肌条呈现开电刺激(on-re-sponse)的舒张波和随后出现的断电刺激(off-response)收缩波,其中产生的开电刺激舒张效应可被L-NNA消除,而断电刺激诱导的收缩效应可被阿托品和胍乙啶(NANC)阻断。在胃底部,Ghrelin和GHRP-6可使开电刺激诱导的平滑肌舒张活动减弱,断电刺激诱导的肌条收缩活动增强,且Ghrelin作用明显强于GHRP-6。L-NNA可显著增强Ghrelin和GHRP-6的促平滑肌收缩效应,但L-AA可显著减弱该作用。在胃窦部,电场刺激肌间神经,舒张波消失,仅出现断电刺激的收缩波。Ghrelin和GHRP-6均可使该收缩作用增强。结论:Ghrelin和GHRP-6均可通过肌间神经丛促进胃底部、胃窦部平滑肌收缩,该效应可能与一氧化氮通路有关。
Objective: To investigate and compare the effects and mechanisms of Ghrelin and its analogues of ghrelin-6 (GHRP-6) on the contraction and contraction of gastric smooth muscle in guinea pigs. Methods: The effects of Ghrelin and GHRP-6 on gastric smooth muscle relaxation and contraction were observed by electric stimulation of the gastric fundus and gastric myenteric nerve in guinea pigs. The effects of nitric oxide synthase (NOS) inhibitor Nω-nitro- L-arginine (L-NNA) and nitric oxide precursor L-arginine (L-AA) on the regulation of gastric smooth muscle activity by Ghrelin and GHRP-6 to elucidate its mechanism. RESULTS: Electrical stimulation of the gastric myenteric nerve at different frequencies (1 ~ 16Hz) resulted in on-re-sponse diastolic and subsequent off-response contractions of the smooth muscle strips, of which The resulting electrical stimulation of relaxation can be abolished by L-NNA, while the de-energized stimulation-induced contractile effect can be blocked by atropine and guanethidine (NANC). Ghrelin and GHRP-6 at the bottom of the stomach could attenuate the relaxation activity of smooth muscle induced by electrical stimulation and the contractile activity of muscle strips induced by electrical stimulation, and the effect of Ghrelin was stronger than that of GHRP-6. L-NNA significantly enhanced the smooth muscle contraction of Ghrelin and GHRP-6, but L-AA significantly attenuated this effect. In the gastric antrum, the electric field stimulates the myenteric nerve, the diastolic wave disappears, and only the contracting wave of the power-off stimulus appears. This contraction was enhanced by both Ghrelin and GHRP-6. CONCLUSION: Both Ghrelin and GHRP-6 can promote the contraction of smooth muscle in gastric fundus and gastric antrum through myenteric plexus, which may be related to the nitric oxide pathway.