Abstract: Objective To investigate the effects of ulinastatin pretreatment on the learning and memory impairment induced by chronic ketamine exposure in juvenile mice. Methods Thirty-six healthy male C57BL/6 mice （weighed 20~30 g） were randomized into three groups：Control group （group C）, ketamine group（group K）, ulinastatin pretreatment group（group S）. In group K and group S, ketamine（per 30 mg/kg）was injected intraperitoneally three times a day at 30-minute intervals for 7 consecutive days, while in Group S, ulinastatin was injected intraperitoneally（per 50000 U/kg）30 minutes before the first injection of ketamine every day. Cognitive test including Morris water maze was carried out 24 hours after the last administration of ketamine. Mice in each group were sacrificed immediately after the test and hippocampi were harvested to determine the expression of tau protein and A β protein using Western blot. Results Compared to group C, the escape latency was prolonged, the time in the original platform were decreased, the frequency of crossing the original platform was decreased, the levels of hippocampal tau protein and Aβ protein were increased in group K（P<0.05）, while in group S, there were no significant differences of above indexes （P>0.05）. Compared to group K, in group S the escape latency was significantly shortened, the time in the original platform were prolonged, the frequency of crossing the original platform was increased, the levels of hippocampal tau protein and Aβprotein were decreased（P<0.05）. Conclusion Cognitive dysfunction induced by chronic ketamine exposure can be reversed by ulinastatin pretreatment in juvenile mice, which may be associated with the down?regulation of the excessive express of hippocampal tau protein and A β protein.

Key words: ketamine, immature mice, ulinastatin, Tau protein, learning and memory, Aβprotein

摘要： 目的　探讨乌司他丁预给药对氯胺酮麻醉后幼鼠认知功能的影响。方法　健康雄性SPF级C57BL/6小鼠36只，21日龄，体重20~30g，采用随机数字表法，将其分为3组（n=12）：空白对照组（C组）、氯胺酮组（K组）、乌司他丁预先给药组（S组）。K组和S组腹腔注射氯胺酮30mg/kg、每隔30min重复注射一次，3次/d，连续7d；S组于每天第1次注射氯胺酮前30min腹腔注射乌司他丁50000U/kg。末次给药结束后24h立即行行为学测试，行为学测试完毕后立即处死大鼠，取海马组织，以westernblot法测定海马tau蛋白、Aβ淀粉肽样蛋白的表达。结果　与C组比较，K组逃避潜伏期延长，原平台停留时间，穿越平台次数减少，海马海马tau蛋白、Aβ淀粉肽样蛋白的表达含量升高（P<0.05），S组上述指标差异无统计学意义（P>0.05）。与K组比较，S组逃避潜伏期明显缩短，原平台停留时间延长，穿越原平台次数增多，海马tau蛋白、Aβ淀粉肽样蛋白的表达降低（P<0.05）。结论　乌司他丁预先给药可改善氯胺酮慢性暴露所致幼鼠认知功能障碍，其机制可能与抑制海马海马tau蛋白、Aβ淀粉肽样蛋白的表达有关。

关键词: 幼鼠, 学习记忆, tau 蛋白, 氯胺酮, A β淀粉肽样蛋白, 乌司他丁