目的探讨褪黑素对异氟醚麻醉诱发老龄大鼠认知功能障碍的影响。方法雄性SD大鼠75只,18~20月龄,体重350~400g,采用随机数字表法,将其随机分为5组(n=15):对照组(c组)吸入含有30%氧气的空氧混合气体4h;异氟醚麻醉组(Ⅰ组)吸入1.5%异氟醚4h;褪黑素5mg/kg组(M1组)、褪黑素10mg/kg组(M2组)、褪黑素20mg/kg组(M,组)分别于麻醉前15min和麻醉开始后3h时腹腔注射褪黑素5、10、20mg/kg(溶解于含1%DMSO的生理盐水中),吸入1.5%异氟醚gh。麻醉结束即刻每组取5只大鼠,进行动脉血气分析,测定血糖水平和海马磷酸化Tau(p-Tau)蛋白的表达。麻醉结束后ldd时,每组取10只大鼠测定认知功能,然后处死大鼠,取海马组织,采用Western blot法检测p-Tau蛋白的表达。结果五组间动脉血气指标和血糖水平差异无统计学意义(P〉0.05)。与c组比较,I组和M1组第3~5天时逃避潜伏期延长,探索时间缩短,海马p-Tau蛋白表达上调(P〈0.05),M2组和M3组逃避潜伏期、探索时间和海马p-Tau蛋白表达差异无统计学意义(P〉0.05);与I组和M1组比较,M2组和M3组第2~5天时逃避潜伏期缩短,探索时间延长,海马p—Tau蛋白表达下调(P〈0.05);I组与M1组间、M2组与M3组间逃避潜伏期、探索时间和海马p-Tau蛋白表达比较差异无统计学意义(P〉0.05)。结论褪黑素(10和20mg/kg)可改善异氟醚麻醉诱发老年大鼠认知功能障碍,其机制可能与其抑制海马Tau蛋白过度磷酸化有关。
Objective To investigate the effect of melatonin on isoflurane anesthesia-induced cognitive dysfunction in aged rats. Methods Seventy-five male SD rats, aged 18-20 months, weighing 350-400 g, were randomly assigned into 5 groups ( n = 15 each) : control group (group C), 1.5% isoflurane group (group I), melatonin 5 mg/kg group ( group M1 ), melatonin 10 mg/kg group ( group M2 ) and melatonin 20 mg/kg group ( group M3 ). Group C inhaled a gas mixture of oxygen and air for 4 h and group I inhaled 1.5 % isoflurane for 4 h. Melatonin 5, 10 and 20 mg/kg (in normal saline containing 1% DMSO) were injected intraperitoneally at 15 min before anesthesia and 3 h after the beginning of anesthesia in groups M, , M2 and M3 respectively, and then the animals inhaled 1.5 % isoflurane for 4- h. At the end of anesthesia, 5 rats in each group were chosen and blood sam- pies were taken to perform arterial blood gas analysis and to detect the blood glucose level and expression of phos- phorylated Tau (p-Tau) protein in hippocampus. Ten rats in each group were chosen at 14 d after the end of anes- thesia and Morris water maze was performed 3 times a day for 5 consecutive days to assess the cognitive function. Then the animals were sacrificed and hippocampi were removed for detection of p-Tau expression by Western blot. Results There were no significant differences in the parameters of arterial blood gas analysis and blood glucose level among the 5 groups ( P 〉 0.05). Compared with group C, the escape latency at 3-5 d was significantly prolonged, the probe time was significantly shortened, and the expression of p-Tau protein was up-regulated in groups I and M1 ( P 〈 0.05), and no significant change was found in the indexes mentioned above in groups M2 and M3 ( P 〉 0.05) . Compared with groups I and M1 , the escape latency at 2-5 d was significantly shortened, the probe time was significantly prolonged, and the expression of p-Tau protein was down-regulated in groups ME and M3 ( P ?