5-HT2A受体在尼可刹米增强新生大鼠延髓脑片呼吸放电中的作用  

Role of 5-HT_(2A) receptor in increase in respiratory-related rhythmic discharge activity by nikethamide in neonatal rat transverse medullary slices

作　　者：千智斌[1] 吴中海[1] 

机构地区：[1]南方医科大学生理学教研室

出　　处：《生理学报》2008年第2期216-220,共5页Acta Physiologica Sinica

基　　金：the National Natural Science Foundation of China(No.30570670);the Natural ScienceFoundation of Guangdong Province(No.5004714)

摘　　要：本文旨在探讨中枢呼吸兴奋剂尼可刹米对新生大鼠基本节律性呼吸的产生和调节的影响及5-HT2A受体在其中的作用。制作新生大鼠离体延髓脑片标本,含面神经后核内侧区（the medial region of the nucleus retrofacialis,mNRF）并保留舌下神经根,灌流改良Kreb＇s液（modified Kreb＇s solution,MKS）,记录舌下神经根呼吸相关节律性放电活动（respiratory-re-lated rhythmic discharge activity,RRDA）,观察不同浓度尼可刹米、5-HT2A受体特异激动剂2,5-二甲氧基-4-碘苯基丙烷[1-（2,5-dimethoxy-4-iodophenyl）-2-aminopropane,DOI]、5-HT2A受体特异拮抗剂酮舍林（ketanserine）以及联合使用尼可刹米和酮舍林对舌下神经根RRDA的影响。结果显示,尼可刹米在0.5-7μg/mL时对延髓脑片RRDA有兴奋作用,在5μg/mL时对吸气时程（inspiratory time,TI）、放电积分幅度（integral amplitude,IA）、呼吸周期（respiratory cycle,RC）等呼吸指标综合效果最显著。DOI明显延长TI、增强IA、缩短RC,对RRDA有兴奋作用。酮舍林明显缩短TI、减弱IA、延长RC,对RRDA有抑制作用。联合使用DOI和酮舍林对RRDA无明显作用。酮舍林可完全阻断尼可刹米对RC的作用,部分阻断尼可刹米对IA的作用,对尼可刹米引起的TI变化无明显影响。结果提示,尼可刹米增强新生大鼠离体延髓脑片舌下神经根RRDA,5-HT2A受体可能是尼可刹米作用途径之一。To investigate the effects of nikethamide on the generation and modulation of rhythmic respiration of neonatal rats and the role of 5-HT2A receptor in this course, experiments were performed on the transverse medullary slices of neonatal rats （both sexes, 1- 3 d） in vitro. The slices containing the medial region of the nucleus retrofacialis （mNRF） with the hypoglossal nerve rootlets were prepared in which the respiratory-related rhythmic discharge activity （RRDA） was recorded from the hypoglossal nerve rootlets by suction electrode. The possible role of nikethamide on RRDA was investigated by administration of an agonist of 5-HT2A receptor, 1-（2,5- dimethoxy-4-iodophenyl）-2-aminopropane （DOI）, and an antagonist of 5-HT2A receptor, ketanserine, dissolved in modified Kreb＇s solution （MKS）. Thirty slices were randomly divided into five groups： Group 1： the slices were perfused with different concentrations of nikethamide （0.5, 1, 3, 5, 7, 10 μg/mL）, and the most effective concentration was selected; Group 2： the slices were perfused with DOI （40 μmol/L）; Group 3： the slices were perfused with ketanserine （40 μmol/L）; Group 4： the slices were perfused with ketanserine ＋ DOI; Group 5： the slices were perfused with nikethamide, then perfused with nikethamide ＋ ketanserine after washout of nikethamide. Nikethamide increased RRDA in transverse medullary slices at 0.5-7 μg/mL, and 5 μg/mL was the most effective concentration. DOI increased RRDA with prolonged inspiratory time （TI）, increased integral amplitude （IA）, and shortened respiratory cycle （RC）. Ketanserine decreased RRDA with shortened TI, decreased IA and prolonged RC. Ketanserine ＋ DOI had no significant effects on RRDA. The effects of nikethamide on RC and IA were totally and partially reversed by additional application of ketanserine, but the effect of nikethamide on TI was not influenced by ketanserine. It is proposed that nikethamide increases RRDA partly via 5-HT2A receptors.

关 键 词：面神经后核内侧区 尼可刹米 5-HT2A受体 延髓脑片 

分 类 号：R338.2[医药卫生—人体生理学]