内源性Orexin-A调控大鼠胃运动的中枢及外周机制

目的:探讨内源性Orexin-A(OXA)对大鼠胃运动的中枢和外周作用机制。方法:选取成年Wistar大鼠为研究对象,通过禁食诱导大鼠合成内源性OXA。血浆OXA浓度采用放射免疫法测定。实验前大鼠注射OXA受体拮抗剂SB334867,观察内源性OXA的作用。迷走神经切断术用来观察迷走神经的介导作用。胃排空采用分光光度法测量,消化间期胃运动通过在胃窦部植入一应力传感器测量。Orexin前体(PPO)在胃和下丘脑组织的表达,采用蛋白印迹确定。结果:禁食18 h后,血浆OXA水平和PPO蛋白表达显著增加(P0.05),在禁食36 h组达到最高水平(P0.01)。内源性OXA促进胃排空(P0.05),抑制消化间期胃蠕动(P0.05)。外周注射SB334867均能阻断上述胃动力效应(P0.05),但对PPO表达没有影响。迷走神经切断术不能阻断内源性OXA的介导作用(P0.05)。结论:禁食能诱导内源性OXA的合成,内源性OXA能加速胃排空,同时它又抑制消化间期胃蠕动。

Effect of Endogenous Orexin-A on Gastric Motility by Central and Peripheral Mechanisms in Rats

Objective:To investigate the central and peripheral effects of endogenous Orexin-A (OXA) on gastric motility in rats.Methods:Selecting adult Wistar rats for the study, the synthesis of endogenous OXA was induced by fasting. Plasma OXA concentration was measured by radioimmunoassay. Rats were pretreated with OXA receptor antagonist SB-334867 prior to measurement to observe the effect of OXA.Vagotomy was used to observe vagus nerve-mediated effects. Gastric emptying was measured by spectrophotometric methods. One strain gauge transducers were attached on the antrum to record interdigestive gastric motility. Preproorexin (PPO) expression in stomach and hypothalamus were tested by Western blot.Results:After fasting 18 h, the level of plasma OXA and PPO protein expression were significantly increased (P <0.05). The highest level of plasma OXA and PPO protein expression appeared in 36h fasting groups (P <0.01). Endogenous OXA promoted gastric emptying (P <0.05), inhibited gastric interdigestive motility (P<0.05). As these effects were abolished with injection of SB-334867, but no effect on PPO expression. Vagotomy surgery did not block endogenous OXA-mediated effects (P> 0.05).Conclusion:Fasting can induce the synthesis of endogenous OXA. Endogenous OXA can accelerate gastric emptying, but it suppressed interdigestive gastric motility.