阿尔茨海默病模型大鼠感觉门控听觉诱发电位P50诱发电位的变化

背景听觉诱发电位P50为反映大脑正常抑制功能的一种直观的脑电生理学指标.目的观察阿尔茨海默病模型大鼠感觉门控听觉诱发电位P50成分的变化.设计随机对照动物实验.单位昆明医学院神经科学研究所.材料选用雌性健康SD大鼠24只,鼠龄4～6月,体质量200～300 g.按随机抽签法将大鼠分为3组实验组、对照组、正常组,每组8只.Morris水迷宫由圆形水池和有机玻璃站台构成,水池分平台、左、右及对侧4个象限.方法实验于2003-09/2005-03在昆明医学院神经科学研究所完成.①实验组切断双侧穹窿海马伞造成阿尔茨海默病模型;对照组切断皮质、胼胝体,但不切断穹窿海马伞;正常组未手术.②在建模后1周对所有大鼠进行包括检测定位航行能力和空间探索能力的水迷宫试验,以确定造模是否成功;每只大鼠每日训练4次,共训练5 d.入池到找到站台的时间(逃避潜伏期)反映定位航行能力;大鼠1 min内在池中搜索站台的游泳轨迹反映空间探索能力.③采用条件(C)-试验(T)双声刺激模式记录听觉P50诱发电位,比较各组大鼠听觉P50诱发电位的差异.计算C-P50波幅、T-P50波幅、T/C比、S2-S1波幅差的绝对值等.计量资料多组间比较用单因素方差分析,组间比较采用t检验.主要观察指标①各组大鼠水迷宫试验,即定位航行能力和空间探索能力检测结果比较.②各组大鼠感觉门控P50诱发电位比较.结果大鼠24只均进入结果分析.①水迷宫试验结果3组大鼠随着训练天数的增加平均潜伏期缩短,前3 d潜伏期均下降,之后趋平稳.实验组潜伏期明显长于正常组和对照组(P＜0.05).正常组和对照组大鼠的游泳轨迹集中在站台象限,站台象限游泳轨迹分别占总游泳轨迹的45.23%和39.7%,与其他象限间游泳轨迹比较,差异明显(P＜0.01).实验组大鼠在站台、右侧、对侧、左侧象限游泳轨迹占总游泳轨迹的28.31%,29.84%,20.47%和21.38%,差异不明显(P＞0.05),游泳轨迹在4个象限中基本呈随机分布.②大鼠感觉门控P50诱发电位检测结果对照组C-P50波幅和S2-S1波幅差的绝对值分别为(21.00±2.85),(15.26±4.07)μV,正常组分别为(17.04±5.32),(10.85±4.24)μV,明显高于实验组(9.67±3.77),(2.89±2.61)μV,P＜0.01].对照组和正常组T-P50波幅与C-P50波幅比值分别为0.25±0.18和0.39±0.16,明显低于实验组(0.92±0.41,P＜0.01).结论①用双侧海马伞切断方法可成功制备阿尔茨海默病动物模型.②双侧海马伞切断阿尔茨海默病模型大鼠存在感觉门控能力的不足.

Changes of auditory evoked potential P50 of sensory gating in model rats with Alzheimer disease

BACKGROUND: Auditory evoked potential P50 (AEP-P50) is a cerebroeilectrophysiological index to directly reflect normal inhibitory function of brain.OBJECTIVE: To observe the changes of AEP-P50 of sensory gating (SG)in model rats with Alzheimer disease (AD).DESIGN: Randomized controlled animal study.SETTING: Neuroscience Institute of Kunming Medical College.MATERIALS: A total of 24 healthy female SD rats, aged 4-6 months,weighing 200-300 g, were randomly divided into experimental group, control group and normal group with 8 in each group. Morris water maze was consisted of round pool and lucite plant. Pool was divided into platform,left, right and bilateral quadrants. METHODS: The experiment was carried out in the Neuroscience Institute of Kunming Medical College from September 2003 to March 2005. ① Experimental group: Bilateral fimbria-fornix was transected to induce AD models; control group: Except fimbria-fornix, cortex and callus were transected; normal group: Rats were not treated with any operation. ② One week after modeling, all rats were tested with Morris water maze which contained localizing navigational ability and spatial seeking ability in order to determine successful models. Each rat was trained 4 times a day for successive 5 days. The duration from putting in pool to finding out platform was regarded as the escape latency (EL) which could reflect localizing navigational ability. Swimming trace of rats which searched platform within 1 minute could reflect spatial seeking ability. ③ AEP-P50 was recorded with "condition (C)-test (T)" auditory double clicks stimuli, additionally,differences of AEP-P50 among the three groups were compared at the same time. C-P50 amplitude, T-P50 amplitude, T/C and absolute value of difference of S2-S1 amplitude were calculated. Measurement data were compared with one-way analysis of variance among groups and with t test intergroup.MAIN OUTCOME MEASURES: ① Morris water maze, I.e., comparison between localizing navigational ability a nd spatial seeking ability; ② comparison of AEP-P50 of rats among three groups.RESULTS: All 24 rats were involved in the fin al analysis. ① results of Morris water maze: With increase of training time, mean latency was shortened. The latency was decreased in the first 3 days and then stabilized gradually. Latency in experimental group was longer than that in normal group and control group (P ＜ 0.05). Swimming traces in normal group and control group were located at platform quadrant, and they were accounted for 45.23% and 39.7% of total quadrant, respectively. There was significant difference as compared with other quadrants (P ＜ 0.01). Swimming traces of rats in experimental group were accounted for 28.31%, 29.84%,20.47% and 21.38% in platform, right, bilateral and left quadrants, respectively; however, there was not significant difference (P ＞ 0.05). Swimming trace was randomly located in four quadrants. ② Results of AEP-P50 of SG: C-P50 amplitude and absolute value of difference of S2-S1 amplitude were (21.00±2.85), (15.26±4.07) μV in control group and (17.04±5.32), (10.85 ±4.24) μV in normal group, which were obviously higher than those in experimental group (9.67±3.77), (2.89±2.61) μV, P ＜ 0.01].T-P50 amplitude and C-P50 amplitude were 0.25±0.18 in control group and 0.39±0.16 in normal group, which were lower than those in experimental group (0.92±0.41, P ＜ 0.01).CONCLUSION: ① Transection of bilateral fimbria-fornix can be used to establish AD animal models successfully. ② AD model rats whose bilateral fimbria-fornix is transected have deficiency of SG.