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

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