利多卡因对小鼠短暂全脑缺血后学习记忆障碍和胆碱能系统损害的影响  

Effect of lidocaine on the impairment of learning and memory function and central cholinergic system after transient global cerebral ischemia in mice

作　　者：宋萍萍[1] 王东信[1] 王沛玉[1] 左萍萍[2] 

机构地区：[1]北京大学第一医院麻醉科,北京100034 [2]中国医学科学院基础医学研究所药理室

出　　处：《北京大学学报（医学版）》2006年第2期164-169,共6页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(30371369)资助~~

摘　　要：目的:观察利多卡因对不同ApoE基因型小鼠短暂全脑缺血后学习记忆障碍和中枢胆碱能系统损害的影响。方法:健康雄性C57BL／6J野生型小鼠(C57小鼠)和ApoE基因敲除型小鼠(ApoE小鼠)各随机分为3组:C57 对照组(假手术操作,不夹闭双侧颈总动脉)C57缺血组(夹闭双侧颈总动脉17 min,经腹腔给予生理盐水)C57利多卡因组(夹闭双侧颈总动脉17 min,经腹腔给予利多卡因)ApoE对照组(处理同C57对照组)ApoE缺血组(处理同C57缺血组)ApoE利多卡因组(处理同C57利多卡因组)。术后恢复7 d,从第8天起进行Morris水迷宫测试,连续5 d。术后第12天水迷宫测试后断头处死大鼠,分离双侧大脑皮层和海马测定乙酰胆碱酯酶、胆碱乙酰基转移酶活性和M受体结合活性。结果:(1)潜伏期:各缺血组均明显长于同品系相应的对照组,C57利多卡因组还明显长于C57缺血组[测试第3天(74．1±32．7)s比(49．2±19．5)s],但ApoE利多卡因组明显短于ApoE缺血组[测试第3～5天分别为(40．7±27．7)s比(84．7±26．8)s,(31．2±19．2)s比(72．1±33．0)s,和(28．0±22．1)s比(60．8 ±26．9)s](P<0．05或0．01)。两品系间比较,ApoE缺血组明显长于C57缺血组,但ApoE利多卡因组明显短于 C57利多卡因组(P<0．05或0．01)。(2)有效搜索策略百分比:各缺血组均明显低于同品系相应的对照组,C57利多卡因组还明显低于C57缺血组[测试第3-5天分别为(18．2±11．7)％比(41．7±17．7)％,(22．7±20．8)％比 (55．6±20．8)％,和(29．6±27．0)％比(66．7±21．7)％],但ApoE利多卡因组明显高于ApoE缺血组[测试第3 -5天分别为(41．7±25．8)％比(15．6±12．9)％,(58．3±20．4)％比(18．8±11．6)％,和(66．7±30．3)％比(28．1 ±20．9)％](P<0．01)。两品系间比较,ApoE缺血组明显低于C57缺血组,但ApoE利多卡因组明显高于C57利多卡因组(P<0．01)。(3)胆碱能系统指标:各缺血组明显低于同品系相应的对照组,C57利多卡ObjectiveL To evaluate the effects of lidocaine on the impairments of learning and memorial function and central cholinergic system after transient global cerebral ischemia in mice of different apolipoprotein E genotypes. Methods： Transient global ischemia was induced by bilateral common carotid arteries occlusion （BCCAO） for 17 minutes. Healthy male C57BL/6J wild-type mice （C57 mice） and apolipoprotein E knockout mice （ApoE mice） were randomly divided into six groups： C57 control group （sham operation, neither BCCAO was performed nor pharmacologic intervention was given）, C57 ischemia group （BCCAO for 17 minutes was performed and normal saline was given intraperitoneally）, C57 lidocaine group （BCCAO for 17 minutes was performed and lidocaine was given intraperitoneally）, ApoE control group （the same procedure as that of C57 control group）, ApoE ischemia group （the same procedure as that of C57 ischemia group）, ApoE lidocaine group （ the same procedure as that of C57 lidocaine group ） . The mice were allowed to recover for 7 days . Morris water maze test were performed from the8th postoperative day. Mice were tested four times daily for 5 consecutive days. The latency periods were recorded and the percentages of effective search strategies were calculated. On the 12th postoperative day after Morris water maze test, mice were decapitated under anesthesia. The cerebral cortex and hippocampus were removed quickly. The activities of acetylcholinesterase （ACHE） and choline acetyltransferase （CHAT） as well as the binding activity of muscarinic receptor （ M receptor） were assayed. Results： （ 1 ） The latency periods were significantly longer in the ischemia groups than in the corresponding control groups （P 〈0.05 or 0.01 ）. They were also significantly longer in C57 lidocaine group than in C57 ischemia group [on the 3rd day of test, （74.1 ±32.7）s vs. （49.2 ± 19.5）s] （P 〈0.05）. However, they were significantly shorter in apoE lidocaine group t

关 键 词：小鼠 基因敲除 脑缺血发作 短暂性 利多卡因 迷宫学习 乙酰胆碱 

分 类 号：R971.2[医药卫生—药品]