右美托咪定逆转七氟烷对发育期大鼠的神经毒性作用  

Influence of dexmedetomidine on sevoflurane-induced neurotoxicity in development-stage rats

作　　者：张甦[1] 刘真真[2] 罗艳[1] 薛庆生[1] 张富军[1] 于布为[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院麻醉科,上海200025 [2]山东大学第二医院麻醉科

出　　处：《上海医学》2013年第2期135-139,共5页Shanghai Medical Journal

基　　金：国家自然科学基金资助项目(30901410)

摘　　要：目的探讨右美托咪定逆转七氟烷对发育期大鼠的神经毒性作用及其可能机制。方法 Sprague-Dawley(SD)大鼠60只,雌雄不拘,日龄7d,体重15～20g,将大鼠随机分入0.9%氯化钠溶液对照组、右美托咪定对照组、七氟烷组和右美托咪定+七氟烷组。0.9%氯化钠溶液对照组、七氟烷组大鼠腹腔注射0.9%氯化钠溶液10μL,放入密闭箱内吸入混合气体(体积分数为0.3的氧气+体积分数为0.7的氮气);右美托咪定、右美托咪定+七氟烷组大鼠腹腔内注射右美托咪定10μL(25μg/kg,以0.9%氯化钠溶液稀释至10μL),放入另一密闭箱内,持续吸入混合气体+体积分数为0.02的七氟烷4h。结束后4h,每组各取6只幼鼠处死取海马组织,采用Western印迹法测定活化型半胱天冬酶3(caspase-3)、磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)的表达水平。各组余下的9只大鼠饲养至42d,采用Morris水迷宫行为学实验测定其学习记忆功能。结果七氟烷组的活化型caspase-3表达水平(0.1373±0.2000)显著高于0.9%氯化钠溶液对照组(0.0694±0.0900,P<0.01),右美托咪定+七氟烷组的活化型caspase-3表达水平(0.0958±0.1300)较七氟烷组显著降低(P<0.05)。七氟烷组的p-p38MAPK表达水平(0.0319±0.2100)显著高于0.9%氯化钠溶液对照组(0.0242±0.1600,P<0.05),右美托咪定+七氟烷组的p-p38MAPK表达水平(0.0210±0.1400)显著低于七氟烷组(P<0.05)。实验第45、46天,七氟烷组大鼠的逃避潜伏期均显著长于0.9%氯化钠溶液对照组同时间(P值均<0.05),而右美托咪定+七氟烷组大鼠均显著短于七氟烷组同时间(P值均<0.05)。七氟烷组的穿越平台次数为(1.33±0.46)次,显著少于0.9%氯化钠溶液对照组的(3.44±0.51)次(P<0.01);右美托咪定+七氟烷组为(1.89±0.86)次,显著多于七氟烷组(P<0.05)。结论右美托咪定可以减轻七氟烷对幼鼠发育期的神经毒性作用,其机制可能与p38丝裂原活化蛋白激酶有关。Objective To investigate the influence of dexmedetomidine on the neurotoxicity induced by sevoflurane in rats and the possible mechanisms. Methods Sixty seven-day-old male and female Sprague- Dawley rats weighing 15- 20 g were randomly divided into normal saline group, dexmedetomidine group, sevoflurane group and dexmedetomidine plus sevoflurane group. The rats in the normal saline group and sevoflurane group were intraperitoneally given 10 pL normal saline and placed in a sealed box to inhale the mixed gas （30% Oz ＋70% N2）. The rats in the dexmedetomidine group and dexmedetomidine plus sevoflurane group were given dexmedetomidine （25 μg/kg, diluted with normal saline to 10 μL） intraperitoneally and placed in another sealed box to inhale the mixed gas containing 2% sevoflurane for 4 h. After 4 hours of disposition, 6 rats in each group were sacrificed to detect the expression of cleaved caspase-3 and p-p38 mitogen activated protein kinase （MAPK） in hippocampus by Western blotting. The rest rats were fed for 42 d, and the cognitive function was tested by Morris water maze. Results Compared with the normal saline group （0. 069 士0. 090 0）, the expression of cleaved caspase-3 in the sevoflurane group （0. 137 3士0. 200 0） was significantly increased （P〈0. 01）.Compared with the sevoflurane group, the expression of cleaved caspase-3 in the dexmedetomidine plus sevoflurane group （0. 095 8士 0. 130 0） was significantly decreased （P〈0.05）. Compared with the normal saline group （0. 024 2 士 0. 160 0）, the expression of p-p38MAPK in the sevoflurane group （0. 031 9 士 0. 210 0） was significantly increased （P〈0.05）. Compared with the sevoflurane group, the expression of p-p38MAPK in the dexmedetomidine plus sevoflurane group （0. 021 0士 0. 140 0） was significantly decreased （P〈0.01）. On day 45 and 46 of the experiment, the escape latency of the sevoflurane group was significantly prolonged compared with the normal saline group （both P 〈 0.05）, and the

关 键 词：右美托咪定 七氟烷 幼鼠 神经毒性 

分 类 号：R965[医药卫生—药理学]