机构地区:[1]华中科技大学同济医学院附属武汉儿童医院临床神经电生理室,武汉430016
出 处:《华中科技大学学报(医学版)》2022年第2期207-211,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基 金:湖北省自然科学基金资助项目(No.2016CFC729);武汉市卫生计生委青年基金资助项目(No.WX17Q26)。
摘 要:目的探讨氧化锂-匹罗卡品(li-pilo)致癫痫大鼠认知障碍与年龄的相关性研究及其可能的致病机制。方法新生SD大鼠在出生后第21天经腹腔注射氯化锂及匹罗卡品,建立癫痫大鼠模型。采用Racine分级评价大鼠癫痫发作行为,选择点燃后出现RacineⅣ级以上表现并存活的大鼠进行实验。造模后根据年龄分为1个月(1 M)、2个月(2 M)及3个月(3 M)癫痫模型,分别通过Morris水迷宫实验观察不同年龄癫痫大鼠的学习记忆功能;应用离体场电位的电生理学方法观察比较不同年龄癫痫大鼠场电位长时程增强(long-term potentiation,LTP)的变化;采用Western blot检测不同年龄癫痫大鼠海马N-甲基-D-天冬氨酸受体2B(NR2B)表达水平。结果(1)水迷宫实验中,1 M癫痫大鼠第1~5天平均潜伏期及运动总路程与年龄匹配对照大鼠相比均无明显改变;2 M癫痫大鼠的第1~3天平均潜伏期及运动总路程与年龄匹配对照大鼠相比无明显改变,第4~5天平均潜伏期及运动总路程显著长于年龄匹配对照大鼠;3 M癫痫大鼠的第1~5天平均潜伏期及运动总路程均显著长于年龄匹配对照大鼠。(2)离体脑片场电位记录显示,高频刺激后癫痫大鼠海马基础场电位斜率与幅值呈现年龄依赖性减弱。(3)Western blot结果显示癫痫大鼠海马NR2B表达水平呈现年龄依赖性降低。结论癫痫大鼠认知障碍程度与年龄相关,其可能机制与NR2B受体表达年龄依赖性降低导致海马LTP年龄依赖性减弱有关。Objective To investigate the correlation between age and cognitive impairment,and the potential pathogenesis.Methods Lithium chloride and pilocarpine were intraperitoneally injected into newborn SD rats on the 21 st day after birth to establish the model of juvenile epileptic rats.The surviving rats with epileptic seizures of grade RacineⅣand above were included in the experiment.Rats were divided into 1 month(1 M model),2 months(2 M model)and 3 months(3 M model)groups according to age.The learning and memory functions of the epileptic rats of different ages were observed through Morris water maze experiment.The electrophysiological method of in vitro field potential was used to observe and compare the changes in long-term potentiation(LTP)in the epileptic rats of different ages.NR2 B-containing N-methyl-D-aspartate receptors(NR2 B)expression levels in hippocampus of the epileptic rats of different ages were detected by Western blotting.Results There were no significant differences in the mean escape latencies as well as the total distance travelled between the 1 M epileptic rats and the control rats;the mean escape latencies and the total distance travelled of 2 M epileptic rats on the 1 st to 3 rd day were not significantly different from those of the control rats,and the mean escape latencies and the total distance travelled of the epileptic rats from the 4 th to 5 th day were significantly increased as compared with those of the control rats.The mean escape latencies and the total distance travelled of the 3 M epileptic rats were significantly higher than that of the control rats from the 1 st to 5 th day.In vitro brain field potential recording showed that after high-frequency stimulation,the slope and amplitude of the field potential in the hippocampal base decreased in an age-dependent manner.Western blotting results showed that the expression level of NR2 B in hippocampus of epileptic rats decreased in an age-dependent manner.Conclusion The age-dependent learning and memory deficits in the li-pilo epile
分 类 号:R742.1[医药卫生—神经病学与精神病学]
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