米诺环素对老龄大鼠海马神经元凋亡及认知功能障碍的影响∗

摘要

Objective To investigate the effect of minocycline on isoflurane-induced hippocampal neuroapoptosis and cognitive dysfunction in aged rats. Methods Forty-five male SD rats were randomly assigned into 3 groups ( n=15): blank control group ( group C) , 1.5% isoflurane group ( group I) and 50 mg��kg-1 minocycline+1.5% isoflurane group ( group M+I) . Minocycline was injected intraperitoneally 12 h before the start of anesthesia for group M+I.Group I and group M+I were exposed to 1.5% isoflurane for 4 h, while group C were exposed to 30% O2-70% N2.At the end of anesthesia, five rats in each group were randomized to analyse arterial blood gas. The other rats in each group were sent back to their home cage until they were fully awake.Fourteen days after anesthesia, Morris water maze was used to assess the cognitive function, and then hippocampi of rats were dissected for detection of the expression of cleaved caspase3, Bax and Bcl-2. Results No difference was found in arterial gas analysis among the 3 groups (P>0.05).Compared with group C, the rats in the group I spent more time locating the platform on the third and fourth training days and the time percentage that the rats in group I spent in the target quadrant was much less (P<0.05).However, these changes were reversed in group M+I (P<0.05).The isoflurane-induced increased level of Bax and cleaved caspase3 and decline of anti-apoptotic factor Bcl-2 were restored by minocycline pretreatment ( P<0.05) . Conclusion Minocycline could attenuate cognitive dysfunction induced by isofluranein aged rats.The mechanism is associated with inhibition of hippocampal neuroapoptosis which is increased by isoflurane.%目的：探讨米诺环素对异氟烷麻醉诱发老龄大鼠海马神经元凋亡和认知功能障碍的影响。方法雄性斯泼累格��多雷( SD)大鼠45只，采用随机数字表法，将其随机分为3组( n＝15)：空白对照组( C组)，异氟烷组( I组)和米诺环素＋异氟烷组( M＋I组)。异氟烷麻醉开始前12 h，M＋I组腹腔注射米诺环素50 mg��kg－1。 C组和I组腹腔注射等量0.9％氯化钠溶液。 C组大鼠给予30％氧气-70％氮气处理4 h，I组和M＋I组1.5％异氟烷处理4 h。麻醉结束后即刻每组各取大鼠5只，进行动脉血气分析。每组其余10只大鼠待完全清醒后，饲养至麻醉后14 d，采用Morris水迷宫检测大鼠的空间学习记忆能力。水迷宫实验后，分离海马，采用Western blot检测cleaved caspase 3、Bax及Bcl-2的表达。结果异氟烷麻醉对各组间大鼠血气分析指标影响差异无统计学意义(P>0.05)。与 C 组比较，I 组大鼠海马区 cleaved caspase3、Bax表达上调，Bcl-2表达下调，第3~4天时大鼠逃避潜伏期延长，目标象限时间比例降低( P<0.05)；与I组比较，M＋I组大鼠海马区cleaved caspase3、Bax表达显著降低，Bcl-2表达显著升高(P<0.05)；第3~4天时大鼠逃避潜伏期缩短，目标象限时间比例升高( P<0.05)。结论米诺环素可以改善异氟烷麻醉所致老龄大鼠学习记忆功能障碍，其机制可能与减轻老龄大鼠海马神经元凋亡有关。