睡眠剥夺对异丙酚麻醉大鼠认知功能的影响

Effect of sleep deprivation on cognitive function in rats undergoing propofoi anesthesia

目的评价睡眠剥夺对异丙酚麻醉大鼠认知功能的影响。方法健康雄性SD大鼠60只，体重200～250g，14～18周龄，采用随机数字表法，将其分为3组（n=20）：正常对照组（C组）、异丙酚麻醉组（P组）和睡眠剥夺＋异丙酚麻醉组（SDP组）。P组静脉注射异丙酚15mg／kg，随后以40mg·kg^-1·h^-1速率输注2h，SDP组快动眼睡眠剥夺24h时实施异丙酚麻醉。分别于睡眠剥夺前、睡眠剥夺后、麻醉后1、3、7d时进行Morris水迷宫实验，记录逃避潜伏期和穿越原平台次数。分别于麻醉后1、7d时取10只大鼠，取脑组织，尼氏染色，光镜下观察海马CA1区神经元形态，采用免疫组化法测定海马CA1区磷酸化Tau蛋白（Tau—pThr^231）表达。结果与C组比较，P组和SDP组麻醉后1d时逃避潜伏期延长，穿越原平台次数减少，海马CA1区Tau-pThr^231表达上调（P〈0．05），SDP组更明显（P〈0．05），其它时点组间比较差异无统计学意义（P〉0．05）；麻醉后1d时SDP组海马CA1区病理学损伤明显重于P组，麻醉后3、7d时SDP组与P组间海马CA1区病理学损伤无明显差异。结论睡眠剥夺可加重异丙酚麻醉大鼠一过性认知功能障碍，其机制与促进Tau蛋白的过度磷酸化有关。

Objective To evaluate the effect of sleep deprivation on cognitive function in the rats undergoing propofol anesthesia. Methods Sixty healthy male Sprague Dawley rats, aged 14-18 weeks, weighing 200-250 g, were randomly assigned into 3 groups （n= 20 each） using a random number table： control group （ group C ） , propofol anesthesia group （ group P ） , and sleep deprivation ＋ propofol anesthesia group （group SDP）. Propofol was given as a bolus of 15 mg/kg followed by an infusion of 40 mg - kg^-1 · h^-1 for 2 h in group P. After the rats were subjected to rapid eye movement sleep deprivation for 24 h, the rats received propofol anesthesia in group SDP. Before sleep deprivation, after sleep deprivation, and at 1, 3 and 7 days after anesthesia, Morris water maze test was used to assess the learning and memory function, and the escape latency and frequency of crossing the original platform were recorded. Ten rats randomly selected from each group at 1 and 7 days after anesthesia were sacrificed, and brains were removed to observe the morphology of nerve cells in the hippocampal CA1 region （by Nissl＇s staining） and to detect the expression of phosphorylated Tau at Thr231 （Tau-pThrTM ） in the hippocampal CA1 region （by immunohistochemisty ）. Results Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the expression of Tau-pThrTMin the hippocampal CA1 region was up-regulated at 1 day after anesthesia in P and SDP groups （P〈0.05） , especially in group SDP （P〈0.05） , and there was no significant difference between the groups at the other time points （P〉0.05）. The pathological changes were aggravated at 1 day after anesthesia in group SDP compared with group P, and there was no significant difference at 3 and 7 days after anesthesia between group SDP and group P. Conclusion Sleep deprivation can aggravate the transient cognitive dysfunction after propofol anesthesia, and the mechanism is related to promotion of Tau phosphorylation in the rats.