大鼠癫痫持续状态后认知功能变化模式及海马脑红蛋白表达水平的实验研究  

Experimental study on the changes of cognitive function and the correlation with neuroglobin expression in rats after status epilepticus

作　　者：张菲菲[1] 程艳伟[1] 于敏敏[1] 石向群[1] 

机构地区：[1]兰州军区兰州总医院神经内科,甘肃省兰州市730050

出　　处：《国际神经病学神经外科学杂志》2017年第5期501-506,共6页Journal of International Neurology and Neurosurgery

摘　　要：目的观察大鼠癫痫持续状态(SE)后学习记忆功能改变情况及海马组织脑红蛋白(NGB)表达水平,探讨癫痫发作对认知功能影响的可能机制。方法健康成年雄性SD大鼠40只,随机分为对照组(n=5)、癫痫模型实验组(n=35),模型组再依据观察时间分为:0 h、1 h、3 h、12 h、24 h、10 d、30 d。应用氯化锂-匹罗卡品(Li-Pilo)建立SE模型,观察致痫期间大鼠行为学变化;采用Nissl染色检测神经元损伤情况;SABC免疫组化法检测NGB表达水平。同时随机选取同期相同品系SD大鼠40只,在造模前及造模后第5d、10 d、15 d、25 d、35 d进行RMT-100迷宫实验,以评价大鼠SE前后学习记忆功能变化情况。结果大鼠SE后,海马CA1、CA3区和DG区均出现不同程度神经元细胞损伤坏死,且NGB表达上调,而海马CA1和CA3区神经元存活数与NGB表达水平呈正相关(r=0.206,P=0.015;r=0.306,P=0.011)。迷宫实验显示工作记忆错误(WME)和参照记忆错误(RME)次数随SE后时间延长均呈递增趋势。相关性分析证实RME次数与CA1和CA3区神经元存活数呈负相关(r=-0.579,P=0.000;r=-0.454,P=0.002),WME次数与CA1和CA3区神经元存活数也呈负相关(r=-0.470,P=0.001;r=-0.507,P=0.000)。结论 SE后NGB表达上调,且与海马组织神经元存活数呈正相关,提示其可能是SE所致缺血缺氧损害的一种代偿神经保护机制。SE后可导致明显认知功能损害,其可能与SE所致海马组织神经元的病理改变相关。Objective To observe the changes of learning and memory function after status epileptics （SE） in rats,and explore the possible mechanism.Methods Intraperitoneal injection Lithium-pilocarpine （Li-Pilo） to establish the rat model of SE.RMT-100 rats eight arm maze test was used to evaluate the learning and memory function before and after epileptic seizure in rats.Nissl staining was used to detect the neuronal damage in hippocampus.Streptavidin-biotin-peroxidase complex immunohistochemical method was used to detect the expression level of NGB.Results After SE,the hippocampal neurons were severely damaged.The expression level of NGB in CA1,CA3 and DG regions were increased,and there was a positive correlation between the number of surviving neurons in CA1,CA3 regions and the NGB expressions （r =0.206,P =0.015;r =0.306,P =0.011）.With the time progress after seizure,the number of working memory error （WME） and reference memory error （RME） increased gradually.And a significant negative correlation between the number of RME and the number of surviving neurons in CA1 and CA3 area （r =-0.579,P =0.000;r =-0.454,P =0.002）.There also was a significant negative correlation between the number of WME and the number of surviving neurons in hippocampal CA1 and CA3 area （r=-0.470,P=0.001;r=-0.507,P=0.000）.Conclusions SE can lead to significant cognitive impairment,which may be related to the pathological changes of hippocampus induced by SE.In addition,the up-regulation of NGB expression in hippocampus after SE may be a compensatory neuroprotective mechanism of ischemic injury induced by epilepsy,and it may be helpful to improve cognitive function.

关 键 词：癫痫持续状态 认知功能 脑红蛋白 八臂迷宫 大鼠 

分 类 号：R742.1[医药卫生—神经病学与精神病学]