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清醒大鼠室旁核灌流谷氨酸受体阻断剂对压力感受性反射的影响

Effect of Antagonism of Glutamate Receptors in the PVN Region on Baroreflex in Conscious Rats

【作者】 崔桂玉

【导师】 金清华;

【作者基本信息】 延边大学 , 生理学, 2007, 硕士

【摘要】 下丘脑室旁核(hypothalamic paraventricular nucleus,PVN)是内分泌系统和自主神经系统的整合中枢,大量研究表明,PVN是调节机体内环境稳态和心血管活动的重要结构。据报道,PVN在正常或应激状态下有着加强心血管活动的作用。但是,这些研究多数是直接或间接刺激PVN后观察了心血管活动的变化,没有对参与心血管活动调节的PVN内的神经递质做进一步的研究,尤其是对PVN参与正常压力感受性反射调节的神经化学机制,还是报道稀少。因此,为了阐明PVN参与正常压力感受性反射调节的部分神经化学机制,本实验在清醒大鼠,静脉注射苯肾上腺素诱发压力感受性反射,同时利用脑部微量透析法和高效液相色谱分析法,观察PVN区谷氨酸Glu(glutamate)含量的变化。其次,通过PVN区灌流谷氨酸受体阻断剂Dizocilpine(MK-801)和6-cyano-7-nitroquinoxaline-2,3-dione(CNQX),进一步探讨了PVN区谷氨酸参与压力感受性反射中枢调节的具体机制。实验结果如下:1.静脉注射苯肾上腺素诱发压力感受性反射,血压由正常的99.5±5.6mmHg上升到149.8±4.3mmHg;心率反射性地从400.8±5.2次/分下降到273.4±6.7次/分(p<0.05)。PVN区细胞外液中谷氨酸水平由正常100%升高到373.44±47.60%(P<0.01)。2.向PVN区灌流谷氨酸受体阻断剂MK-801或CNQX(100μmol/L)20分钟,同时静脉给予与对照组相同剂量的苯肾上腺素诱发压力感受性反射。和对照组相比,阻断剂使用组比较,血压升高的幅度明显减少(P<0.01),而心率下降的幅度却明显升高(P<0.01),导致压力感受性反射的敏感性ΔHR/ΔMAP明显增加(P<0.01)。结论:室旁核区的谷氨酸可能是通过离子型谷氨酸受体参与压力感受性反射的中枢调节,而且其作用可能是抑制性的。

【Abstract】 The hypothalamic paraventricular nucleus (PVN) is a central site for the integration of the endocrine system and the autonomic nervous system,and a number of studies have shown that the PVN is an important structures for the regulation of body-fluid homeostasis and the central control of cardiovascular function.Though some studies have shown that the PVN enhance the cardiovascular responses induced by direct or indirect stimulation of PVN, but the neurochemical mediators in the PVN responsible for mediating baroreflex are not well understood.Therefore,the objective of this study is to investigate the possible involvement of glutamate (Glu) in the paraventricular nucleus (PVN) in the central regulation of baroreflex.The baroreflex was induced by intravenous injection of phenylephfine in conscious rats,and the extracellular concentration of Glu in the PVN region was measured by microdialysis and high performance liquid chromatography (HPLC) techniques.Next,to determined whether the observed Glu release was involved in the baroreflex,NMDA (N-methyl-D-aspartate) and non-NMDA receptor antagonists,MK-801 (dizocilpine) and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione),were perfused in the PVN region during baroreflex.Our results are as follows:1.The intravenous injection of phenylephrine increased the blood pressure (BP) from 99.5±5.6 mmHg to 149.8±4.3 mmHg,and the heart rate (HR) was reflexly decreased from 400.8+5.2 beat/min to 273.4±6.7 beat/min,(p<0.05);the Glu concentration in the PVN region immediately increased from basal level 100%to 373.44±47.60% (P<0.01) .2.MK-801 and CNQX (1001.tmol/L) were perfused in the PVN for 20min,and the baroreflex was induced by intravenous injection of phenylephrine.Both glutamate receptors antagonists reduced phenylephrine-induced BP increase (p<0.01),and enhanced the decrease of HR (p<0.01),resulting a significant increase in baroreflex sensitivity (P<0.01) .Conclusion:Glutamate in PVN is involved in central regulation of baroreflex,which may inhibit baroreflex via ionothopic glutamate receptors,and the effect is inhibited.

  • 【网络出版投稿人】 延边大学
  • 【网络出版年期】2007年 06期
  • 【分类号】Q4
  • 【下载频次】40
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