七氟醚对不同性别大鼠海马神经元p-CREB1表达的影响  

Is there any difference in the effects of sevoflurane inhalation on hippocampal neuronal phosphorylated cAMP response element-binding protein between male and female rats

作　　者：祭高明[1] 谢红[1] 张力元[1] 胡丽芳[2] 孙锐[1] 王琛[1] 

机构地区：[1]苏州大学附属第二医院麻醉科,215004 [2]苏州大学神经科学研究所,215004

出　　处：《中华麻醉学杂志》2011年第8期964-967,共4页Chinese Journal of Anesthesiology

基　　金：江苏省研究生创新计划（CX10b-55Z）

摘　　要：目的评价七氟醚对不同性别大鼠海马神经元磷酸化cAMP反应元件结合蛋白1（p-CREB1）表达的影响。方法健康成年雌性SD大鼠30只，3月龄，体重180．220g，采用随机数字表法，将大鼠随机分为2组（n=15）：对照组（Fc组）和七氟醚组（Fs组）；健康成年雄性sD大鼠28只，3月龄，体重380～440g，采用随机数字表法，将大鼠随机分为2组（n=14）：对照组（Mc组）和七氟醚组（Ms组）。Fc组和Mc组吸入95％氧气（流量4L／min）2h，Fs组和Ms组吸入3％七氟醚2h。于停止吸入七氟醚后2d时行避暗实验；于停止吸入七氟醚后3—7d时行Morris水迷宫实验，第7天认知功能测定结束后处死大鼠，取脑组织，剥离海马，采用Western blot法检测海马组织p-CREB1及Bcl-2、caspase-8的表达水平。结果与Fc组比较，Fs组停止吸人七氟醚后3d时逃避潜伏期延长，游泳总路程增加，海马组织p-CREB1和Bcl-2表达下调，caspase-8表达上调（P〈0．05）；与Mc组比较，Ms组停止吸入七氟醚后3—6d时逃避潜伏期延长，游泳总路程增加，海马组织p-CREBl和Bcl-2表达下调，caspase-8表达上调（P〈0．05）；与Fs组比较，Ms组停止吸入七氟醚后4—6d时逃避潜伏期延长，游泳总路程增加，海马组织p-CREB1和Bcl-2表达下调（P〈0．05）。结论七氟醚可通过抑制海马神经元CREB1蛋白磷酸化，上调caspase-8蛋白表达，下调Bcl-2蛋白表达，促进神经元凋亡，导致大鼠认知功能减退，且对雄性大鼠的效应更明显。Objective To investigate the difference in the effects of sevoflurane inhalation on hippocampal neuronal phosphorylated cAMP response element-binding protein between male and female rats. Methods Fiftyeight healthy SD rats aged 3 months weighing 180-440 g were randomly divided into 4 groups： group female control （Fc group, n = 15） ; group female sevoflurane （Fs group, n = 15） ; group male control （Mc group, n = 14） and group male sevoflurane （Ms group, n = 14）. The 2 control groups （Fc group, Mc group） inhaled 95% 02 for 2 h, while the 2 sevoflurane groups （Fs group, Ms group） inhaled 3% sevoflurane for 2 h. The cognitive function was assessed by passive avoidance task performed on the 2nd day after sevoflurane inhalation and Morris water maze test once a day for 5 consecutive days from day 3-7 after sevoflurane. The animals were sacrificed after last cognitive function assessment test on the 7th day after sevoflurane inhalation and their brains were removed for determination of expression of hippocampal neuronal p-CREB1, Bcl-2 and caspase-8 protein expression. Results Sevoflurane in- halation significantly increased the escape latency and swimming distance at day 3 after sevoflurane inhalation in group Fs and at days 3-6 in group Ms as compared with their control groups （Fc group, Mc group） in Morris water maze test. The escape latency and swimming distance were significantly longer at 4-6 d in Ms group than in Fs group. Sevoflurane significantly decreased p-CREB1 and Bcl-2 protein expression and increased caspase-8 expres- sion in groups Fs and Ms as compared with their control groups （Fc group, Mc group）. Bcl-2 protein expression was significantly higher in group Fs than in group Ms. Conclusion Two hour 3 % sevoflurane inhalation can in- duce hippocampal neuronal apoptosis by down-regulating CREB1 phosphorylation and Bcl-2 expression and up-regulating caspase-8 expression. The effects are greater in male rats than in female rats.

关 键 词：麻醉药 吸入 性别因素 CAMP反应元件结合蛋白质 海马 神经元 

分 类 号：R965.3[医药卫生—药理学]