摘要
目的探讨七氟醚麻醉对淀粉样前体蛋白（APP）转基因小鼠认知功能及海马神经元tau蛋白磷酸化水平的影响。方法雄性APP基因突变小鼠，体重18～22g，8～12周龄，取APP转基因阳性（APP^＋）小鼠44只，采用随机数字表法，将其分为2组：七氟醚组（AS组，n=28）和对照组（AC组，n=16）；取APP阴性（APP）小鼠44只，采用随机数字表法，将其分为2组：七氟醚组（S组，n=28）和对照组（C组，n=16）。AS组和S组吸入3％七氟醚4h，AC组和C组吸入纯氧4h。吸入七氟醚或纯氧后24h，进行水迷宫实验。AC组和C组于吸入纯氧后1d（T1）时，AS组和S组于吸入七氟醚后1、3和7d（T1-3）时采用Western blot法检测海马神经元tau蛋白Ser262位点[tau（S262）]和Ser396位点[tau（S396）]的磷酸化水平。结果与C组比较，S组和AC组潜伏期延长，平台所在原象限停留时间百分比降低，S组tau（S262）和AS组tau（S262）、tau（S396）磷酸化水平增强（P〈0．05）；与S组比较，AS组潜伏期延长，平台所在原象限停留时间百分比降低，tau（S262）和tau（S396）磷酸化水平增强（P〈0．05）；与AC组比较，AS组潜伏期延长，平台所在原象限停留时间百分比降低，tau（S262）和tau（S396）磷酸化水平增强（P〈0．05）。结论七氟醚麻醉可加重APP^＋小鼠认知功能损伤，其机制与增强海马神经元tau（S262）和Tau（S396）磷酸化水平有关。
Objective To investigate the effect of sevoflurane anesthesia on the cognitive function and phosphorylation of tau in hippoeampal neurons in amyloid precursor protein （APP） transgenic mice. Methods Male APP gene mutation mice, weighing 18-22 g, aged 8-12 weeks, were used in the study. Forty-four APP positive mice were randomly divided into 2 groups （n = 10 each） ： sevoflurane group （group AS, n = 28） and control group （group AC, n = 16） . Forty-four APP negative mice were randomly divided into 2 groups： sevoflurane group （group S, n = 28） and control group （group C, n = 16） . Animals in groups S and AS inhaled 3% sevoflurane for 4 h. While in groups C and AC, animals inhaled pure oxygen for 4 h. Morris water maze was performed 24 h after sevoflurane or pure oxygen inhalation. The phosphorylation of tau at Ser262 and Ser396 was detected by Western blot on 1 day after pure oxygen inhalation （Tl ） in groups AC and C, and on 1, 3 and 7 days after sevoilurane inhalation in groups AS and S. Results Compared with group C, the escape latency was significantly prolonged and the duration of staying at the original platform quadrant was shortened in groups S and AC, and the phosphorylation of tau at Ser262 in group S and phosphorylation of tau at Ser262 and Ser396 in group AS were increased （ P 〈 0.05 ）. Compared with group S, the escape latency was significantly prolonged, the duration of staying at the original platform quadrant was shortened and the phosphorylation of tau at Ser262 and Ser396 was increased in group AS （ P 〈 0.05）. Compared with group AC, the escape latency was significantly prolonged, the duration of staying at the original platform quadrant was shortened and the phosphorylation of tau at Ser262 and Ser396 was increased in group AS （ P 〈 0.05）. Conclusion Sevoflurane anesthesia can aggravate the impairment of cognitive function in APP positive mice and the increase in the phosphorylation of tau at Ser262 and Ser396 is involved in the mechanism.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2012年第12期1433-1436,共4页
Chinese Journal of Anesthesiology
