乌司他丁预先给药对氯胺酮慢性暴露致幼鼠认知功能障碍的影响  

Effects of ulinastatin pretreatment on cognitive dysfunction induced by chronic exposure to ketamine in immature mice

作　　者：洪玉[1] 王寿平[1] 彭书崚[1] 刘婷[1] 陈英圳[1] 周礼生[1] 周立兵[2] 

机构地区：[1]中山大学孙逸仙纪念医院麻醉科, 广州市510120 [2]暨南大学-香港大学脑功能与健康联合实验室

出　　处：《中华麻醉学杂志》2014年第2期143-146,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金面上项目（81271223）;广东省自然科学基金（S2012010009065）

摘　　要：目的 评价乌司他丁预先给药对氯胺酮慢性暴露致幼鼠认知功能障碍的影响.方法 健康雄性SPF级C57BL/6小鼠36只,21日龄,体重20 ～ 30 g,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）和乌司他丁预先给药组（U组）.K组和U组腹腔注射氯胺酮30 mg/kg,每隔30 min重复注射1次,3次/d,连续21 d;U组于每天第1次注射氯胺酮前30 min时腹腔注射乌司他丁50000U/kg.末次给药结束后24h进行认知功能测试,包括Morris水迷宫和旷场实验测试,认知功能测试完毕后立即处死,取海马组织,采用ELISA法测定海马IL-1、IL-6、TNF-α含量.结果 与C组比较,K组逃避潜伏期延长,原平台象限停留时间和旷场中心区停留时间缩短,穿越原平台象限次数减少,海马IL-1、IL-6、TNF-α含量升高（P＜0.05）,U组上述指标差异无统计学意义（P＞0.05）.与K组比较,U组逃避潜伏期缩短,原平台象限停留时间和旷场中心区停留时间延长,穿越原平台象限次数增多,海马IL-1、IL-6、TNF-α含量降低（P＜0.05）.结论 乌司他丁预先给药可改善氯胺酮慢性暴露致幼鼠认知功能障碍,其机制可能与抑制海马炎性反应有关.Objective To evaluate the effects of ulinastatin pretreatment on cognitive dysfunction induced by chronic exposure to ketamine in immature mice.Methods Thirty-six healthy male C57BL/6 mice,aged 21 days,weighing 20-30 g,were randomly divided into 3 groups （n =12 each） using a random number table：control group （group C）,ketamine group （group K）,and ulinastatin pretreatment group （group U）.In K and U groups,ketamine 30 mg/kg was injected intraperitoneally three times a day at 30-minute intervals for 21 consecutive days,while in group U,ulinastatin 50 000 U/kg was injected intraperitoneally at 30 min before the first injection of ketamine everyday.Cognitive function was assessed using Morris water maze and open field tests at 24 h after the last administration of ketamine.Mice in each group were sacrificed immediately after the end of the tests and hippocampi were harvested to determine the contents of interleukin-6 （IL-6）,IL-1 and tumor necrosis factor-α （TNF-α） using ELISA.Results Compared with group C,the escape latency was significantly prolonged,the time spent in the original platform and in the central area for the open field was shortened,the frequency of crossing the original platform was decreased,and the contents of IL-1,IL-6,and TNF-α were increased in group K （P 〈 0.05）,while there were no significant differences in the indexes mentioned above in group U （P 〉 0.05）.Compared with group K,the escape latency was significantly shortened,the time spent in the original platform and in the central area for the open field was prolonged,the frequency of crossing the original platform was increased,and the contents of IL-1,IL-6,and TNF-α were decreased in group U （P 〈 0.05）.Conclusion Ulinastatin pretreatment can improve cognitive dysfunction induced by chronic exposure to ketamine in immature mice,and inhibition of inflammatory responses in hippocampi may be involved in the mechanism.

关 键 词：胰蛋白酶抑制剂 氯胺酮 认知障碍 青少年 

分 类 号：R614[医药卫生—麻醉学]