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幼鼠惊厥持续状态脑损伤时依达拉奉的神经保护作用
陈秀丽, 李光乾
温州医科大学附属育英儿童医院神经内科
摘要:
目的 观察幼年大鼠惊厥持续状态后海马CA1区神经细胞损伤的情况,探讨依达拉奉对惊厥性脑损伤是否具有保护作用。方法 采用随机数字表法将195只幼年大鼠分为3组,依达拉奉组、惊厥持续状态组和对照组,每组65只,各组再按处死时间点不同分为4、12、24、48和72h5个亚组,每个亚组13只。采用氯化锂-匹罗卡品法制作惊厥持续状态模型,使用依达拉奉进行干预,并观察各组幼年大鼠出现惊厥发作的行为学表现;利用HE染色观察幼年大鼠脑神经元病理形态,电镜观察海马CA1区超微结构变化,原位末端标记(TUNEL)法观察神经元凋亡情况。结果两组大鼠5级惊厥率和平均惊厥潜伏期比较差异有统计学意义(P<0.05);与对照组相比,惊厥持续状态组和依达拉奉组12、24、48和72h海马CA1区TUNEL阳性细胞数差异均有统计学意义(P<0.01);在惊厥持续状态后,依达拉奉组12、24、48和72h海马CA1区TUNEL阳性细胞数均较惊厥持续状态组下降(P<0.01),但在4h,两组比较差异无统计学意义(P>0.05)。结论惊厥持续状态可导致幼年大鼠海马神经元损伤,依达拉奉预处理能减轻幼年大鼠惊厥持续状态后海马神经元损伤程度,提示依达拉奉对幼年大鼠惊厥持续状态后脑损伤具有一定的保护作用。
关键词:  海马 惊厥持续状态 惊厥性脑损伤 依达拉奉 凋亡
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Neuroprotective effect of edaravone pretreatment on hippocampal neuron in juvenile rats with status convulsion
CHEN Xiuli, LI Guangqian
Yuying Children Hospital,Wenzhou Medical University
Abstract:
Objective To investigate the neuroprotective effect of edaravone (ED) on neuron in hippocampal CA1 re- gion of juvenile rats after status convulsion (SC). Methods One hundred and ninety five male Sprague-Dawley rats aged 19d were randomly divided into normal saline pretreatment group(NS group), status convulsive group(SC group)and edaravone treat- ment group (ED group) with 65 in each group; and 15 animals in each group were sacrificed at 4,12,24,48 and 72h after SC in- duction, respectively. SC was induced by intraperitoneal injection of lithium chloride and pilocarpine; the rats in ED and NS groups were pretreated with edaravone and normal saline, respectively. Then the histopathology changes in hippocampus were viewed by light microscope,the ultrastructural changes of hippocampal CA1 region were observed by electron microscope and the cell apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL), Results The convulsion latency in ED group prolonged, and the rate 5-grade seizure declined compared with two control groups (P<0.05). SC group showed different degrees of degeneration and loss of neurons at all time points, and the pathological changes were the most significant in 48 h af- ter SC. The histopathology in ED group also showed that the degrees of degeneration and cell death were attenuated, the loss of neuron reduced, compared with SC group at corresponding time points. Electron microscopy showed that the neuronal nuclei in CA1 area presented mild pycnosis, nuclear membrane fuzzy and irregular and mitochondria vacuolization, which was marked at 48h after SC. The pathological damage of hippocampus in ED group was alleviated compared to SC group at each time points. TUNEL results showed that the TUNEL-positive cells were significantly increased in hippocampal CA1 area at 12 h after SC in SC group and reached at peak in 48h. The trend in ED group was similar to that in SC group, compared with SC group, the TUNEL-positive cells were significantly decreased at 12, 24, 48 and 72h (P<0.01). Conclusion SC can induce the neuronal cell injudy in hippocampus of juvenile rats. ED pretreatment can attenuate the degree of hippocampal region injury, which indicates that edaravone exerts neuroprotective effect for immature rats from brain damage after SC.
Key words:  Hippocampus Status convulsion Convulsion-induced brain injury Edaravone apoptosis