米诺环素对氯胺酮慢性暴露致小鼠认知功能障碍的影响  

Effects of Minocycline on Cognitive Dysfunction Induced by Chronic Ketamine Exposure in Mice

作　　者：王寿平[1] 陈晓彤[2] 

机构地区：[1]广州医科大学附属第三医院麻醉科,510150 [2]中山大学孙逸仙纪念医院博济医疗中心,510120

出　　处：《岭南急诊医学杂志》2015年第4期262-263,277,共3页Lingnan Journal of Emergency Medicine

基　　金：广东省自然科学基金(S2012010009065;2014A030313112);国家自然科学基金面上项目(81271223)

摘　　要：目的:评价米诺环素对氯胺酮慢性暴露致小鼠认知功能障碍的影响。方法:健康雄性SPF级C57BL/6小鼠30只,21日龄,体重约23 g,分为3组(n=10):空白对照组(C组)、氯胺酮组(K组)、米诺环素预先给药组(M组)。K组和M组腹腔注射氯胺酮30 mg/kg、每隔30 min重复注射一次,3次/d,连续21 d;M组于每天第1次注射氯胺酮前1 h腹腔注射米诺环素50 mg/kg。末次给药结束后24 h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小鼠,取海马组织,以酶联免疫吸附(ELISA)法,测定海马IL-1、IL-6、TNF-α的含量。结果:与C组比较,K组逃避潜伏期延长,原平台停留时间和旷场中心区停留时间缩短,穿越平台次数减少,海马IL-1、IL-6、TNF-α含量升高(P<0.05),M组上述指标差异无统计学意义(P>0.05)。与K组比较,M组逃避潜伏期明显缩短,原平台停留时间和旷场中心区停留时间延长,穿越原平台次数增多,海马IL-1、IL-6、TNF-α含量降低(P<0.05)。结论:米诺环素可改善氯胺酮慢性暴露所致小鼠认知功能障碍,其机制可能与抑制中枢炎性反应有关。Objective： To investigate the effects of Minocycline on the cognitive dysfunction induced by chronic ketamine exposure in mice. Methods：30 male C57BL/6 mice were randomly divided into three groups（n=10）：Control group （group C）,ketamine group （group K）,Minocycline pretreatment group （group M）.In group K and group M, ketamine （per 30 mg/kg） was injected intraperitoneally three times a day at 30-minute intervals for 21 consecutive days,while in Group M,Minocycline was injected intraperitoneally （50 mg/kg）1 h before the first injection of ketamine every day. Cognitive test including Morris water maze and Openfield test was carried out 24 h 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 inflammatory cytokines including IL-6,IL-1 and TNF-α using ELISA. Results：Compared to group C,the escape latency was prolonged, the time in the original platform and central area in openfield were decreased ,the frequency of crossing the original platform was decreased,and the levels of hippocampal IL-1, IL-6, TNF-α were increased in group K （P〈0.05）, while in group M ,there were no significant differences in the above indexes （P〉0.05）. Compared to group K, the escape latency was significantly shortened, the time spent in the original platform and central area in openfield were prolonged , the frequency of crossing the original platform was increased, and the levels of hippocampal IL-1,IL-6, TNF-α were decreased in group M （P〈0.05）. Conclusion：Minocycline can improve cognitive dysfunction induced by chronic ketamine exposure,and inhibition of neuroinflammation reponse may be involved in the mechanism.

关 键 词：氯胺酮 米诺环素 认知障碍 神经炎性 

分 类 号：R614[医药卫生—麻醉学]