异丙酚对新生大鼠离体延髓自发节律性呼吸放电的作用

The effect of propofol on the spontanous rhythmical respiratory discharges in the isolated medulla-spinal cord preparation of newborn rats

目的 观察异丙酚对延髓基本呼吸节律中枢自发节律性呼吸放电的作用并探讨其可能的机制。方法 制备 5 6只新生SD大鼠 (0～ 3d)离体延髓 脊髓标本 ,改良的Krebs液 (MKS)恒温灌流 ,随机分成Ⅰ～Ⅶ组 (每组n =8)。Ⅰ组为空白对照组 (MKS组 ) ,Ⅱ～Ⅵ组异丙酚浓度分别为5 μmol L、2 0 μmol L、5 0 μmol L、10 0 μmol L和 2 5 0 μmol L持续灌流 3min ,第Ⅶ组先给GABAA受体特异性阻断剂荷包牡丹 2 0 μmol L ,然后异丙酚 2 0 μmol L灌流 3min ,观察给药后 1、3、5、10、15、30min时神经腹根自发节律性呼吸放电 (SRRD)的活动。结果 1)Ⅰ组各时间点SRRD各项指标均无显著性变化 (P >0 0 5 )。 2 )Ⅱ～Ⅵ组与给药前比 :给药后 1 3minⅡ～Ⅴ组SRRD的频率增快、呼气时间缩短 ,5 10minⅡ～Ⅵ组SRRD频率随浓度增大显著减慢、呼气时间显著延长 ,第Ⅵ组 15min时 8只中有7只停止 ;Ⅱ～Ⅵ组SRRD的吸气时间无显著变化 ;SRRD放电强度 (IAD)给药后 3 5minⅡ组增强 ,Ⅲ～Ⅵ组减弱 ,10 15min时Ⅲ、Ⅳ组增强而第Ⅵ组仍减弱直至SRRD停止。 3)荷包牡丹硷 异丙酚 (Bic Pro)组SRRD给药前后无显著变化。结论 1)异丙酚对新生大鼠离体延髓 脊髓标本SRRD具有浓度依赖性抑制作用 ,且以SRRD的呼气时间延长效应为主。 2 )

Objective To investigate the effects of propofol on the spontanous rhythmical respiratory discharges (SRRDs) in the isolated medulla spinal cord preparation of newborn rats and its possible mechanism Methods Newborn SD rats (0 3 days) of either sex were used Isolated medulla spinal cord preparation was made according to the method of Suzue, et al Brain stem was severed between medulla and pons and spinal cord was severed between cervical and thoracic segments Efforts were made to keep the ventral root of the cervical spinal nerves of possible, while the medulla spinal cord preparation was being removed The medulla spinal cord preparation was placed with the ventral side facing up in the bath continuously perfused with modified Krebs solution (MKS)(3 4ml/min,T=27℃, pH=7 3 7 4, 95% O 2 5% CO 2) glass adsorb electrodes containing Ag AgCl needle were attached to the rentral root of C 4 or C 5 spinal nerve SRRD were recorded, Forty eitht isolated medulla spinal cord preparations were divided into 7 groups: groupⅠ: control group in which preparation was perfused with MKS only; groupⅡ Ⅳ: propofol groups in which preparation was perfused continuously for 3 min with different concentrations of propofol (5, 20, 50, 100, 250 μmol/L); group Ⅶ: bicuculine propofol group in which preparation was continuously perfuse for 3min with a specific GABAA receptor blocker, bicuculine (20μmol/L) followed by perfusion of propofol(20μmol/L) for another 3 min SRRDs were recorded before and 1, 3, 5, 10, 15, and 30 min after propofol or bicuculine propofol perfusion Results 1) In control group, there was no significant change in SRRDs at the designated time internals 2) In group Ⅱ Ⅵ after propofol perfusion, the bursts of SRRDs were inhibited in a concentration dependent manner, but at 1 3 min SRRD showed a temporary excitation (frequency increased and expiratory time became shorter), at 5 min frequency began to slow down and expiratory time became prolonged, at 15 min in 7 out of preparations were stopped in group Ⅵ (propofol 250 μmol/L) Inspiratory time did not change significantly after propofol in all propofol groups, but integral area of discharge (IAD) of SRRD showed some enlargement until SRRDs stopped 3) with bicuculine(20 μmol/L) pretreatment, SRRDs did not change significantly after perfusion with propofol (20 μmol/L) Conclusions Propofol inhibits SRRDs in a conecntration dependent manner as shown by prolongation of expiratory time GABAA receptor may play an important role in inhibitory action of propofol on the isolated medulla spinal cord preparation from newborn rats