麻醉药物对新西兰兔钟基因Clock和Bmal1表达的影响

Effect of anesthesia on the expression of clock gene Clock and Bmal1 in New Zealand rabbits

目的:观察麻醉药物对新西兰兔钟基因Clock和Bmal1表达的影响,并探讨其变化规律。方法:将90只新西兰兔随机分为生理盐水组(S组,1 mL/h)、丙泊酚组[P组,600μg/(kg·min^(-1)),1 mL/h]、10%的脂肪乳组(F组,1 mL/h)、右美托咪定组[D组,1μg/(kg·min^(-1)),1 mL/h]、七氟烷(sevoflurane,SEV)组(吸入2.5%SEV,SEV组),每组18只。24 h后停止吸入或静脉滴注麻醉药。5组试验动物分别在停止麻醉后0、24和72 h处死,分离脑组织。采用蛋白质印迹法测定新西兰兔Clock和Bmal1蛋白的表达水平。结果:麻醉后0和24 h,与S组比较,SEV组、P组和D组中Clock和Bmal1蛋白表达水平均明显下调(均P<0.05)。麻醉后72 h,与S组比较,SEV组、P组和D组中Clock和Bmal1蛋白表达水平均无明显变化(均P>0.05)。与S组比较,F组中各时间点的Clock和Bmal1蛋白表达水平均无明显变化(均P>0.05)。结论:麻醉药物SEV、丙泊酚和右美托咪定可抑制新西兰兔脑组织中Clock和Bmal1蛋白的表达,这种抑制作用一直持续至麻醉后24 h,而在麻醉后72 h该抑制作用明显减弱。

Objective:To evaluate the effect of anesthetic drugs on the expression of circadian gene Clock and Bmal1 in the brain of New Zealand rabbits,and to explore their change pattern.Methods:A total of 90 New Zealand rabbits were randomly divided into 5 groups(n=18 in each group):A normal saline group(1 mL/h saline,group S),a propofol group[600μg/(kg·min^(-1))propofol,1 mL/h,group P],a 10%lipid group(1 mL/h lipid,group F),a dexmedetomidine group[1μg/(kg·min^(-1))dexmedetomidine,1 mL/h,group D),a sevoflurane(SEV)group(2.5%SEV,SEV group).Inhaled and intravenous anesthetic drugs were stopped after 24 h.Experimental animals were killed at 0,24,and 72 h after anesthesia,and their brain tissues were isolated.Western blotting was performed to measure the Clock and Bmal1 protein expression in the brain of rabbits.Results:At 0 and 24 h after anesthesia,compared with the group S,the levels of Clock and Bmal1 proteins were decreased significantly in the group P,the group D,and the group SEV(all P<0.05).At 72 h after anesthesia,compared with the group S,the levels of Clock and Bmal1 proteins showed no significant changes in the group P,the group D,and the SEV group(all P>0.05).Compared with the group S,the levels of Clock and Bmal1 proteins at all time points showed no significant changes in the group F(all P>0.05).Conclusion:Anesthetic SEV,propofol,and dexmedetomidine can inhibit the expression of clock gene Clock and Bmal1 protein in the brain fissues of the New Zealand rabbits,and the suppression effect continues for at least 24 h after anesthesia,whereas the suppression decreases significantly at 72 h after anesthesia.