七氟醚对不同性别大鼠海马神经元p-CREB1表达的影响

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180～220 g,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380-440 g,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4 L/min)2 h,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组停止吸入七氟醚后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-CREB1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.

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

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 inhalation 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 expression 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 induce 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.