A68930对新生鼠离体延髓脑片呼吸节律性放电的影响

Effects of A68930 on rhythmical respiratory discharge in isolated neonatal rat brainstem slice

目的探讨激活多巴胺D1受体对延髓脑片基本节律性呼吸放电的影响。方法用SPF级新生SD大鼠(0～3d)制备离体延髓脑片标本,随机分成Ⅰ～Ⅳ组(每组n=5),以改良的Kreb's液恒温灌流,稳定记录到与之相连的舌下神经根的呼吸节律性放电活动(RRDA)。Ⅰ组为对照组,只用Kreb's液灌注;Ⅱ～Ⅳ为实验组,分别给予1、2、5μmol/L的多巴胺D1受体特异性激动剂cis-(±)-1-(aminomethyl)-3,4-dihydro-3-phenyl-1H-2-benzopyran-5,6-diolhydrochlo-ride(A68930)持续灌流10min;观察各组改灌前以及改灌后1、3、5min时舌下神经的呼吸节律性放电活动的变化。结果(1)给药后RRDA的呼吸周期(RC)和呼气时间(TE)随时间延长逐渐缩短,放电积分幅度(IA)逐渐增大,5min时RC、TE和IA的变化最明显;在2、5μmol/L组与用药前比较三项指标有统计学差异(2μmol/L组1min时的IA与用药前相比较没有统计学差异);(2)随用药浓度增大RC、TE逐渐减小,而IA逐渐增大,5μmol/L时RC、TE、IA变化最明显;用2、5μmol/L的A68930灌流后,三项指标与对照组比较有统计学差异。结论多巴胺D1受体参与节律性呼吸的调节;多巴胺D1受体可能主要是通过缩短呼气时程增加呼吸的频率,通过增强吸气放电幅度来参与呼吸运动强度的调节。

Objective To investigate the role ofdopamine-1 receptor in the modulation of basic respiration rhythm. Methods Newborn SD rat （0-3 days, n=20） brain stem slices containing the medial region of the nucleus retrofacialis （mNRF） were prepared with the hypoglossal nerve roots retained. The respiratory rhythmical discharge activity （RRDA）of the hypoglossal nerve was recorded using suction electrodes on these preparations, and the effects of dopamine-1 receptor on RRDA were investigated by application of the specific agonist of dopamine-1 receptor A68930 at different concentrations （0, 1, 2, and 5 μmol/L） in the perfusion solution. Results The respiratory cycles （RC） and the expiratory time （TE） decreased progressively with gradual increment of the integrated amplitude （IA） after A68930 administration, and their changes were the most conspicuous at 5 min after the administration. A68930 at the concentrations of 2 and 5 μmol/L resulted in the most obvious changes in RC, TE, and IA （P〈0.05）, but IA exhibited no significant variation at 1 min after perfusion with 2μmol/L A68930 （P〉0.05）. RC and TE were gradually shortened after treatment with increasing concentrations of A68930, which also caused gradual increment oflA, and at the concentration of 5 μmol/L, RC, TE, and IA all showed the most obvious changes （P〈0.01）. Conclusions Dopamine-1 receptor plays a role in the modulation of RRDA in isolated neonatal rat brainstem slice. A68930 may increase the frequency of respiration by shortening TE and enhance the respiratory activity by increasing the amplitude of inspiratory discharge of the respiratory neurons.