时辰对丙泊酚、羟丁酸钠、依托咪酯催眠ED_(50)和LD_(50)的影响

Effect of circadian rhythm on the hypnotic ED_(50) and LD_(50) induced by propofol,sodium oxybate and etomidate

目的观察不同时辰对丙泊酚、羟丁酸钠和依托咪酯催眠半数有效量(ED50)和半数致死量(LD50)的影响。方法昆明种小鼠270只,雌雄不拘,随机分为丙泊酚组、羟丁酸钠组和依托咪酯组3大组,每大组再分为ED50组和LD50组,分别于8:00、14:00和21:00静脉注射丙泊酚、羟丁酸钠或依托咪酯,应用序贯法实验,测定并计算各药物催眠ED50和LD50。结果丙泊酚在14:00的催眠ED50和LD50高于8:00和21:00(P<0.05),8:00和21:00的催眠ED50和LD50均相似(P>0.05);羟丁酸钠和依托咪酯在14:00的催眠ED50低于8:00与21:00(P<0.01),而8:00和21:00的催眠ED50相似(P>0.05),羟丁酸钠和依托咪酯的各时间点的LD50均相似(P>0.05)。结论丙泊酚、羟丁酸钠和依托咪酯的催眠作用以及丙泊酚的LD50均具有时辰依赖性。

Objective To observe the effects of circadian rhythm on the median effective dose（ED50） and median lethal dose（LD50） included by anesthetics（propofol,sodium oxybate and etomidate）.Methods 270 mice were randomized into 3 large（propofol,sodium oxybate and etomidate） groups,with each group subdivided into ED50 and LD50 groups,and each smaller group was further divided into 3 subgroups（n=15 each）.Propofol,sodium oxybate and etomidate were intravenously injected at 8：00,14：00 and 21：00,respectively.The hypnotic ED50 and LD50 at different time points were determined by up-down sequential allocation in mice.Results The hypnotic ED50 and LD50 of propofol at 14：00 were significantly larger than those at 8：00 and 21：00（P0.05）.The hypnotic ED50 and LD50 of propofol at 8：00 were similar to those at 21：00（P0.05）.The hypnotic ED50 values of sodium oxybate and etomidate at 14：00 were significantly smaller than those at 8：00 and 21：00（P0.01）,while the hypnotic ED50 values at 8：00 and 21：00 were similar.The LD50 values of sodium oxybate and etomidate at each time point were similar,respectively（P0.05）.Conclusion The hypnotic effects of propofol,sodium oxybate and etomidate as well as the LD50 of propofol were circadian-dependent.