褪黑素对蛛网膜下腔出血后继发性脑损伤及认知功能的影响及其机制研究  

Research on the Effects and Mechanisms of Melatonin on the Secondary brain Damage and Neurobehavioral Dysfunction after Experimental Subarachnoid Hemorrhage

作　　者：吴凌云[1] 王中[1] 陈罡[1] 季骋远 王伟[1] 

机构地区：[1]苏州大学附属第一医院神经外科,江苏苏州215006

出　　处：《现代生物医学进展》2014年第15期2823-2826,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81100872)

摘　　要：目的:探讨褪黑素对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后神经元细胞凋亡、坏死及继发性认知功能障碍的影响。方法:选择80只成年健康雄性SD大鼠,随机分为四组:正常组(n=20)、单纯SAH组(n=20)、SAH+安慰剂治疗组(n=20)和SAH+褪黑素治疗组(n=20),经大鼠自体尾动脉(股动脉)非肝素化动脉血在20 s内注入视交叉池建立蛛网膜下腔出血模型,褪黑素注射剂量为150 mg/kg,1次/12 h,在蛛网膜下腔出血建模后48h处死各组部分大鼠,取血凝块周围的皮层脑组织(额颞底)做标本,通过TUNEL荧光染色及Fluoro-Jade B荧光染色测定神经元凋亡及坏死的情况,各组剩余大鼠在SAH后48小时开始通过Morris水迷宫试验测试其认知功能。结果:SAH组大鼠的活动功能评分、Morris水迷宫试验的逃避潜伏期及总路程、神经元细胞凋亡和坏死的百分比均较正常对照组大鼠显著升高(P<0.01),而褪黑素治疗组以上指标均显著低于安慰剂治疗组(P<0.05),但SAH组和安慰剂组之间以上指标比较均无统计学意义(P>0.05)。结论:褪黑素可能通过减少神经元细胞的凋亡和坏死改善蛛网膜下腔出血后大鼠的认知功能障碍。Objective： To investigate the effects and mechanisms of melatonin on the secondary brain damage and neurobehavio- ral dysftmction after experimental subarachnoid hemorrhage （SAH）. Methods： 80 adult SD rats were divided into four groups： control group （n=20）, SAH group （n=20）, SAH＋vehicle group （n=20）, and SAH＋melatonin group （n=20）. The rat SAH model was induced by injection of 0.3 ml fresh arterial, nonheparinized blood into the prechiasmatic cistern in 20 s. In SAH＋melatonin group, melatonin was administered i.p. at 150 mg/kg at 0, 12, 24 and 36 hr after the induction of SAH. Part of rats in each group were killed on 48 hr after SAH.The brain sample was removed and keeped in 10% formalin solution.Cognitive and memory changes were investigated in the Morris water maze at 48 hr after the induction of SAH with the rest of rats in each group. Results： The behavior and activity scores, escape laten- cy and swimming distance in Morris water maze task, apoptosis and necrosis percentage of neurons of SAH rats were all significantly higher than those of the contol rats （P〈0.01）, while the above index of SAH＋melatonin group were significantly lower than those of the SAH＋vehicle rats （P〈0.05）, but no significant difference was found in the above index between SAH and SAH＋vehicle rats（P〉0.05）. Conclusion： Melatonin may improve the neurobehavioral dysfunction after SAH through decreasing the apoptosis and necrosis of neu- rons.

关 键 词：蛛网膜下腔出血 褪黑素 脑损伤 Morris水迷宫试验 认知功能 

分 类 号：Q95-3[生物学—动物学] R743.35[医药卫生—神经病学与精神病学]