组胺H1和H2受体在新生大鼠离体延髓脑片呼吸节律性放电调节中的作用

本研究探讨组胺H1和H2受体在新生大鼠基本节律性呼吸的发生和调节中的作用.以改良的Kreb's液恒温灌流新生Sprague-Dawley大鼠离体延髓脑片标本,稳定记录与之相连舌下神经根的呼吸节律性放电活动(respiratory-related rhythmical discharge activity, RRDA).实验分为5组:第1、2、3组分别单独给予组胺(histamine, HA)、 H1受体特异阻断剂pyrilamine和H2受体特异阻断剂cimetidine;第4组分别先后给予HA和HA pyrilamine;第5组分别先后给予HA和HA cimetidine,观察舌下神经根RRDA的变化.结果显示,单独给予HA后呼吸周期(respiratory cycle, RC)及呼气时程(expiratory time, TE)明显缩短,而吸气时程(inspiratory time, TI)及放电积分幅度(integral amplitude, IA)无明显变化;给予pyrilamine后RC、 TE明显延长,TI、 IA也无明显变化,且HA的作用可以被pyrilamine逆转;给予cimetidine后RC、 TE、 TI、 IA均无明显变化,且HA的作用不能被cimetidine逆转.结果提示,H1受体参与哺乳动物基本呼吸节律的产生和调节,H2受体对哺乳动物基本节律性呼吸的调控无明显影响.

Role of histamine H(1) and H(2) receptors in the modulation of respiratory rhythmical discharge in medulla oblongata slice preparation of neonatal rats

The present study was carried out to determine the role of histamine H(1) and H(2) receptors in the generation of basic respiratory rhythm. Neonatal (aged 0-3 d) Sprague-Dawley rats of either sex were used. The medulla oblongata slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O2 and 5% CO2), and ended in 3 min. Respiratory rhythmical discharge activity (RRDA) of the rootlets of hypoglossal nerve was recorded by suction electrode. Thirty medulla oblongata slice preparations were divided into 5 groups. In groups I, II and III, histamine (5 mumol/L), H(1) receptor specific antagonist pyrilamine (10 mumol/L) and H(2) receptor specific antagonist cimetidine (5 mumol/L) was added into the perfusion solution for 15 min separately. In group IV, after application of histamine for 15 min, additional pyrilamine was added into the perfusion for another 15 min. In group V, after application of histamine for 15 min, additional cimetidine was added into the perfusion for another 15 min. The discharges of the roots of hypoglossal nerve were recorded. Signals were amplified and band-pass filtered (100-3.3 kHz). Data were sampled (1-10 kHz) and stored in the computer via BL-420 biological signal processing system. Our results showed that histamine significantly decreased the respiratory cycle (RC) and expiratory time (TE), but changes of integral amplitude (IA) and inspiratory time (TI) were not statistically significant. Pyrilamine induced significant increases in RC and TE, but changes of TI and IA were not statistically significant. Cimetidine had no effects on RC, TE, TI and IA of RRDA. The effect of histamine on the respiratory rhythm was reversed by additional application of pyrilamine but not cimetidine. Taken together, with the results mentioned above, histamine H(1) receptors but not H(2) receptors may play an important role in the modulation of RRDA in the medulla oblongata slice preparation of neonatal rats.