异氟醚麻醉对老龄大鼠海马β淀粉样蛋白生成、c—Jun氨基末端激酶和环磷酸腺苷反应元件结合蛋白磷酸化的影响  

Effects of isoflurane anesthesia on β-amyloid protein generation and phosphorylation of c-dun N-terminal kinase and cyclic AMP responsive element binding protein in hippocampus of aged rats

作　　者：倪诚[1] 谭刚[2] 周阳[1] 钱敏[1] 罗爱伦[2] 刘亚杰[1] 汤义[1] 李刚[1] 李民[1] 郭向阳[1] 

机构地区：[1]北京大学第三医院麻醉科,100191 [2]中国医学科学院北京协和医学院北京协和医院麻醉科

出　　处：《中华麻醉学杂志》2013年第1期13-16,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（30972835）

摘　　要：目的探讨异氟醚麻醉对老龄大鼠海马β淀粉样蛋白（Aβ）生成、c-Jun氨基末端激酶（JNK）和环磷酸腺苷反应元件结合蛋白（CREB）磷酸化的影响。方法雄性sD大鼠96只，18月龄，体重450—500g，采用随机数字表法，将其分为3组：正常对照组（C组）、1％异氟醚麻醉组（S．组）和2％异氟醚麻醉组（s2组）。S。组和S：组分别吸入1％和2％异氟醚4h。每组取12只大鼠，麻醉后1d行Morris水迷宫实验，每组分别于麻醉后1d（T1）、7d（T7）取12只大鼠，行旷场反应实验，旷场反应实验结束后，处死大鼠，取海马组织，采用Westernblot法测定邯、磷酸化JNK（p-JNK）和磷酸化CREB（p-CREB）的表达。结果与C组比较，S1组和S2组逃避潜伏期延长，原平台象限探索时间比减少，S1组T1时总运动距离、离开边界距离和内环内距离延长，海马组织郎表达上调，p-CREB表达下调，T7时离开边界距离和内环内距离延长，海马组织邯表达上调，S2组，T1时总运动距离、快速运动距离、离开边界距离延长和内环内距离延长，海马组织邶表达上调，p-JNK表达上调，p-CREB表达下调，T7时总运动距离、快速运动距离、离开边界距离延长和内环内距离延长，海马组织邮表达上调（P〈0．05或0．01）。结论异氟醚麻醉导致老龄大鼠认知功能减退的原因与其促进海马邯生成、JNK激活和抑制CREB激活有关。Objective To investigate the effects of isoflurane anesthesia on β-amyloid protein （Aβ） generation and phosphorylation of c-Jun N-terminal kinase （JNK） and cyclic AMP responsive element binding protein （CREB） in the hippocampus of aged rats. Methods Ninety-six male Sprague-Dawley rats, aged 18 months, weighing 450-500 g, were randomly divided into control group （group C, n = 24）, 1% isoflurane anesthesia group （group S1, n = 36） and 2% isoflurane anesthesia group （group S2, n = 36）. Groups S1 and S2 inhaled 1% and 2% isoflurane for 4 h, respectively. Twelve rats were chosen in each group and Morris water maze was performed 1 day after anesthesia. Twelve rats in each group were chosen on day 1 and 7 after anesthesia （T1 , T7 ） and open field test was performed. The rats were sacrificed after open field test and hippocampi were isolated for determination of the expression of Aβ, phosphorylated JNK （p-JNK） and phosphorylated CREB （p-CREB） in hippocampal tissues by Western blot. Results Compared with group C, the escape latency was significantly prolonged and target quadrant dwell time ratio was decreased significantly in groups S1 and $2 , the total movement distance, leave border distance and inner toroid distance were prolonged, Aβ expression was up-regulated, and p-CREB expression was down-regulated at Tl and leave border distance and inner toroid distance were prolonged, Aβ expression was up-regulated at T7 in group S1 , and the total movement distance, faster movement distance, leave border distance and inner toroid distance were prolonged, the expression of Aβ and p-JNK was up-regulated, and p-CREB expression was down-regulated at TI , and the total movement distance, faster movement distance, leave border distance and inner toroid distance were prolonged, the expression of Aβ was up-regulated at T7 in group S2 （ P 〈 0.05 or 0.01 ）. Conclusion The mechanism by which isoflurane anesthesia induces cognitive dysfunction is related to promotion of Aβ generation and

关 键 词：异氟醚 海马 淀粉样Β蛋白 丝裂原激活蛋白激酶类 CAMP反应元件结合蛋白质 老年人 

分 类 号：R614[医药卫生—麻醉学]