GABAA受体在尼可刹米引起的新生大鼠呼吸兴奋中的作用  

GABA_A receptor participates in respiratory enhancement induced by nikethamide in neonatal rats

作　　者：千智斌[1] 齐莹[1] 吴中海[1] 

机构地区：[1]南方医科大学生理学教研室

出　　处：《南方医科大学学报》2008年第3期301-304,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(30570670);广东省自然科学基金(5004714)~~

摘　　要：目的探讨γ-氨基丁酸A(GABAA)受体在尼可刹米引起的新生大鼠呼吸兴奋中的作用。方法制作新生大鼠离体延髓脑片标本,包含面神经后核内侧区并保留舌下神经根,给予灌流改良Krebs液,记录舌下神经根的呼吸相关节律性放电活动(RRDA)。实验分为5组:第1组分别以浓度为0.5、1.0、3.0、5.0、7.0、10.0μg/ml尼可刹米灌流脑片,观察舌下神经根RRDA的变化,做出尼可刹米的量效曲线并选择最适浓度;第2组以浓度为10、20、40、60μmol/L的GABA灌流脑片,观察RRDA的变化做出量效曲线选择最适浓度;第3组以10μmol/L荷牡丹碱灌流脑片;第4组联合应用40μmol/LGABA和10μmol/L荷牡丹碱灌流脑片;第5组5μg/ml尼可刹米灌流脑片产生明显作用后冲洗至RRDA基本恢复,再联合灌流5μg/ml尼可刹米和10μmol/L荷牡丹碱。结果尼可刹米浓度在0.5￣7.0μg/ml对延髓脑片RRDA有兴奋作用,5μg/ml时对吸气时程(TI)、放电幅度积分(IA)、呼吸周期(RC)等呼吸指标综合效果最显著。GABA在40μmol/L对RRDA放电的TI、IA、RC抑制作用最显著。荷牡丹碱对TI、IA、RC均有兴奋作用。联合使用GABA和荷牡丹碱,RRDA与对照组相比无显著改变。联合使用尼可刹米和荷牡丹碱,与单独使用尼可刹米相比TI、IA显著增强,RC无显著改变。结论尼可刹米能够增强新生大鼠离体脑片舌下神经根RRDA,GABAA受体可能是尼可刹米作用途径之一。Objective To investigate the role of GABAA receptor in nikethamide-induced respiratory enhancement in the medullary slices of neonatal rats. Methods Ex vivo medullary slices of neonatal rats （1 to 3 days old） containing the medial region of the nucleus retrofacialis with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb＇s solution to record respiration-related rhythmic discharge activity （RRDA） fi＇om the hypoglossal nerve rootlets using suction electrodes. Thirty RRDA-positive slices were randomized into 5 equal groups and perfused with nikethamide （at concentrations of 0.5, 1, 3, 5, 7, and 10 μg/ml with the optimal nikethamide concentration determined）, GABA （at 10, 20, 40, and 60μmol/L to determine the optimal concentration）, 10 μmol/L bicuculline, 10 μmol/L bicuculline plus 40 μmol/L GABA, and 5 μg/ml nikethamide followed by 5 p,g/ml nikethamide plus 10 μ mol/L bicuculline atter wash out, respectively. Results Nikethamide increased RRDA at the concentrations of 0.5-7 μg/ml, and 5 μg/ml nikethamide showed the most distinct effect on the inspiratory time （TO, integral amplitude （IA）, and respiratory cycle （RC）. GABA at 40μmol/L showed the most effective inhibition of RRDA in terms ofTI, IA, and RC. Bicuculline at 10 μmol/L could increase the IA, TI and RC, but the combination of 10μmol/L bicuculline and 40 μmol/L GABA had no significant effects on RRDA. Compared with nikethamide used alone, nikethamide plus bicuculline significantly increased TI and IA without affecting RC. Conclusion Nikethamide can enhance RRDA of the hypoglossal nerve rootlets in the medullary slices of neonatal rats, and the effect can be partially mediated by the GABAA receptor.

关 键 词：面神经后核内侧区 尼可刹米 GABAA受体 延髓脑片 

分 类 号：R96[医药卫生—药理学]