异丙酚对大脑皮层突触体谷氨酸释放的影响

Effects of propofol on glutamate release in rat cerebrocortical synaptosomes

目的 探讨异丙酚的麻醉作用机理。方法 分别制备１０只成年ＳＤ大鼠大脑皮层突触体。实验分为ＫＣｌ组（突触体悬液中均加入２０ｍ ｍ ｏｌ·ｍ ｌ－ １ＫＣｌ）和氨基吡啶组（突触体悬液中加入６．７ｍ ｍ ｏｌ·ｍ ｌ－ １ 氨基吡啶）。每组又分为５ 个亚组，分别对应于突触体悬液中异丙酚浓度为０、１２．５、２５、５０ 和１００μｍ ｏｌ·ｍ ｌ－ １。谷氨酸的释放量由连续酶标荧光法测定。结果 异丙酚对ＫＣｌ组突触体谷氨酸释放量无显著抑制作用；而对氨基吡啶组突触体谷氨酸则有显著抑制作用，且呈剂量依赖性。结论 ＫＣｌ和氨基吡啶作用的差别仅在于ＫＣｌ不引起Ｎａ＋ 通道开放，而氨基吡啶则导致Ｎａ＋ 通道开放。异丙酚对两组突触体谷氨酸释放的不同影响表明，异丙酚主要通过阻断Ｎａ＋ 通道开放，减少中枢神经系统主要的兴奋性神经递质谷氨酸的释放而产生麻醉效能。

Objective To investigate the anesthetic mechanism of propofol.Methods Synaptosomes were purified from 10 adult SD rats were divided into KCl group: the resuspended synaptosomes containing 20 mmol·ml -1 KCl,and 4 aminopyridine group:the resuspended synaptosomes containing 6.7 mmol·ml -1 4 aminopyridine.Either group was divided into 5 subgroups.0,12.5,25,50,and 100μmol·ml -1 of propofol were added to the resuspended synaptosomes of subgroups,respectively.Glutamate release in each subgroup was measured by continuous fluremetry.Results There were no significant inhibitory actions of propofol on the glutamate release from synaptosomes in each subgroup of KCl group.Significant and dose dependent inhibition of glutamate release occurred in each subgroup of 4 aminopyridine group.Conclusion: KCl depolarizes the plasma membrane with inactivated Na + channels,while 4 aminopyridine destabilizes the membrane potential with activated Na + channels.So the major excitatory neurotransmitter glutamate release inhibited by propofol through blocking Na + channels may be the main anesthetic action mechanism of propofol.