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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(P<0.05),在禁食36 h组达到最高水平(P<0.01)。内源性OXA促进胃排空(P<0.05),抑制消化间期胃蠕动(P<0.05)。外周注射SB334867均能阻断上述胃动力效应(P<0.05),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(P>0.05)。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。
Objective: To investigate the central and peripheral mechanism of endogenous Orexin-A (OXA) on gastric motility in rats. Methods: Adult Wistar rats were selected as experimental subjects and endogenous OXA was induced by fasting in rats. Plasma OXA concentrations were measured by radioimmunoassay. Before experiment, rats were injected with OXA receptor antagonist SB334867 to observe the effect of endogenous OXA. Vagus nerve transection is used to observe the mediation of the vagus nerve. Gastric emptying was measured spectrophotometrically and the inter-gastric gastric motility was measured by implanting a stress sensor in the antrum. Expression of Orexin precursor (PPO) in gastric and hypothalamus tissues, as determined by Western blotting. RESULTS: After fasting for 18 h, the levels of plasma OXA and PPO protein were significantly increased (P <0.05), and reached the highest level at 36 h of fasting (P <0.01). Endogenous OXA promoted gastric emptying (P <0.05) and inhibited gastric motility during the interdigestive period (P <0.05). Peripheral injection of SB334867 could block the gastric motility effect (P <0.05), but had no effect on PPO expression. Vagotomy did not block the mediation of endogenous OXA (P> 0.05). Conclusion: Fasting can induce the synthesis of endogenous OXA. Endogenous OXA can accelerate gastric emptying, meanwhile, it inhibits gastric motility during the interdigestive period.