美金刚减轻异氟烷麻醉引起的老年小鼠认知功能障碍

Effect of Memantine on Isoflurane-induced Cognitive Dysfunction in Aged Mice

目的研究异氟烷麻醉对老年小鼠神经行为和学习记忆能力的影响,并探讨其可能的机制及美金刚的保护作用。方法 60只45周龄的雄性C57BL/6小鼠随机分成3组:对照组(Con)、异氟烷组(Iso)、美金刚+异氟烷组(Mem+Iso)。Con组的小鼠仅吸入氧气2h,Iso组的小鼠吸入混合1.5%异氟烷的氧气2h,Mem+Iso组小鼠在吸入异氟烷前2h,以8mg/kg美金刚灌胃,Con组和Iso组小鼠用等量生理盐水灌胃。在异氟烷处理后12h时每组取10只小鼠分离海马组织进行Western blot检测磷酸化-tau(P-tau)蛋白表达,ELISA法检测IL-1β水平。异氟烷处理后48h剩余小鼠进行Morris水迷宫实验。结果与Con组比较,Iso组小鼠空间学习记忆能力明显下降,海马P-tau表达上调,IL-1β水平明显增加(均P<0.05);与Con组比较,Mem+Iso组小鼠空间学习记忆能力、海马P-tau表达、IL-1β水平差异无统计学意义(均P>0.05);与Iso组相比,Mem+Iso组小鼠空间学习能力明显增强,海马内P-tau表达下调,IL-1β水平明显减少(均P<0.05)。结论异氟烷麻醉能使老龄小鼠发生认知功能障碍,引起海马P-tau、IL-1β水平增加;而美金刚可改善其行为认知损害,下调P-tau、IL-1β表达,对异氟烷麻醉引起老年小鼠认知功能障碍具有保护作用。

Objective To evaluate the effect of Memantine on isoflurane-induced cognitive dysfunction in aged mice.Methods Sixty male C57BL/6mice were randomly divided into 3groups：control group（Con）,Isoflurane group（Iso）and memantine＋isoflurane group（Mem＋Iso）（n=20in each）.The mice in all isoflurane-treated groups were exposed to oxygen mixed with 1.5%isoflurane for 2h.The mice in Con group were exposed to oxygen only for 2h.The Mem＋ Iso group mice were given memantine（8mg/kg）by intragastric administration 2hbefore exposure to 1.5% isoflurane.The mice in the Con and Iso group were given saline water by intragastric administration.Mice treated with isoflurane were tested in the Morris water maze,in which the latency to the platform and the proportion of time spent in the target quadrant were recorded 48 hafter exposure to 1.5%isoflurane.Fresh cerebral hippocampi were dissected to measure the protein expression of P-tau by Western blotting,and the content of IL-1βwas analyzed by ELISA 12 hafter isoflurane exposure.Results Compared with Con group,the latency to the platform was significantly prolonged,and the proportion of time spent in the target quadrant was decreased significantly and the levels of P-tau and IL-1βincreased in the Iso group（all P〈0.05）.Compared with Iso group,the latency to the platform was significantly decreased,the proportion of time spent in the target quadrant was significantly prolonged,the expression of P-tau and IL-1βsignificantly decreased in the Mem＋Iso group（all P〈0.05）.Conclusion Isoflurane can induce cognitive dysfunction in aged mice and elevate the level of P-tau and IL-1βin the hippocampus.Memantine can improve cognitive dysfunction and decrease the level of P-tau and IL-1βin aged mice.