膈下迷走神经切断对大鼠中枢nesfatin-1抑酸作用的影响

Effect of vagotomy on central nesfatin-1-induced decrease in gastric acid secretion

目的:探讨双侧膈下迷走神经切断对侧脑室注射nesfatin-1的抑酸作用的影响.方法:♂SD大鼠,侧脑室置管后,每只大鼠分别给予侧脑室注射1、5和50 pmol的nesfatin-1及等体积的灭菌水(5μL/rat),于2 h后处死大鼠,收集胃液,测定其胃酸的变化,用实时定量PCR检测(real-time quantitative PCR,qRT-PCR)检测胃黏膜中H^+/K^+-ATPase mRNA的表达、测定酶的活性.另外,将侧脑室成功置管的♂SD大鼠分成迷走神经切断组和假手术组,每组分别给予nesfatin-1(50pmol)及等体积的灭菌水(5μL/rat),于2 h后处死大鼠,观察迷走神经切断术对nesfatin-1引起的胃酸变化的影响.结果:大鼠侧脑室注射浓度为5 pmol和50pmol的nesfatin-1后2 h,大鼠胃酸分泌减少,其中50 pmol作用最强(P<0.05).同时大鼠胃黏膜中H^+/K^+-ATPase mRNA的表达和活性受到抑制(P<0.05).另外,对大鼠行膈下迷走神经切断术,侧脑室注射nesfatin-1引起的胃酸分泌的减少以及H^+/K^+-ATPase mRNA的表达和活性的下降等效应也消失,与对照组相比差异无统计学意义(P>0.05).结论:侧脑室注射nesfatin-1可呈剂量依赖性地抑制大鼠胃酸的分泌,这一效应可能是通过激活迷走神经途径实现的.

AIM：To observe the effect of gastric acid secretion decrease induced by intracerebroventricular（ICV）injection of nesfatin-1.METHODS：Male Sprague-Dawley rats were randomly and equally divided into a control group and a nesfatin-1 group after implantation of an ICV cannula.The nesfatin-1 group was injected intracerebroventricularly with different concentrations of nesfatin-1,and the control group was treated with the same amount of distilled water（5 μL/rat）.The volume of gastric secretion was measured and the amount of gastric acid was determined by titration with NaOH.H7 IC-ATPase mRNA expression was detected by real-time quantitative PCR.Activity of HV ICATPase was determined indirectly by measuring K~＋-stimulated p-nitrophenyl phosphatase（pNPPase） activity.In another group of animals,rats were divided into a vagotomy and a sham group.The treatments and measurements were the same as above.RESULTS：Intracerebroventricular infusion of nesfatin-1 significantly reduced gastric acid output,and the maximum inhibitory effect on gastric acid output was detected at a dose of 50pmol/ rat.Furthermore,nesfatin-1 decreased H~＋/K~＋-ATPase mRNA expression and activity in gastric mucosal tissue compared to the control group.The inhibitory action of nesfatin-1 on the acid output and H~＋/K~＋-ATPase expression and activity was abolished by vagotomy.CONCLUSION：Nesfatin-1 injected intracerebroventricularly induces a dosedependent decrease in gastric acid secretion in rats and the vagal nerve may be involved in the process of the effect of nesfatin-1.