帕金森病模型大鼠学习记忆能力变化的观察

Abstract

[目的]利用Morris水迷宫、避暗箱、穿梭箱检测6-羟多巴胺(6-OHDA)致帕金森病(PD)模型大鼠学习记忆的能力，了解PD除行为障碍外的认知变化，并运用大鼠脑内酪氨酸羟化酶(tyrosine hydroxylase, TH)表达量检测的方法来对PD大鼠模型进行检验和评价。[方法]实验分为PD模型组和正常对照组。首先以立体定位单侧纹状体注射6-OHDA法制备PD大鼠模型，2周后腹腔注射阿扑吗啡(APO)诱导转圈，旋转圈数 > 7 r/min的大鼠判定为成功PD模型，并运用大鼠脑内酪氨酸羟化酶(tyrosine hydroxylase, TH)表达量检测的方法来对PD大鼠模型进行检验和评价。应用Morris水迷宫测定大鼠的目标象限游泳路程及目标象限游泳时间；采用大鼠避暗箱进行多次测试法，获取并分析明箱观察时间百分比(%)数据；应用大鼠穿梭箱进行穿梭箱被动回避反应，获取并分析主动逃避次数(次)和主动逃避平均时间(秒)。[结果] PD模型组大鼠和正常对照组相比，Morris水迷宫实验中，象限游泳路程显著减少(p < 0.05)，目标象限游泳时间极显著减少(p < 0.01)；避暗箱进行多次测试法中，明箱观察时间百分比(%)明显缩短(p < 0.05)；穿梭箱被动回避反应实验中，主动逃避次数(次)和主动逃避平均时间(秒)均明显减少(p < 0.05)。[结论] 6-OHDA纹状体注射构建的PD大鼠的学习记忆能力明显降低，可以作为研究人类帕金森病性痴呆的模型。 [Aim] To evaluate the learning and memory impairment in rat model of Parkinson disease (PD) which established by injection of 6-hydroxydopamine (6-OH) at different stages with Morris maze, passive avoidance test and active avoidance test. [Methods] Rats were grouped into two: PD model rats and Normal rats. The unilateral stereotaxic intra-striatal single point injection of 6-hydroxy- dopamine (6-OH) was adopted to establish PD model rats. The rats were induced to rotate by in-jecting apomorphine (APO) while 2 weeks after operation, in order to screen the successful PD rat model. The number of rotations for the successful PD model rats is greater than 7 r/min. Measuring the distance and the time that the rats stayed the quadrant of the platform with Morris maze. Application of rats box for the shuttle box passive avoidance response, acquisition and analysis of the number of active escapes and takes the initiative to escape the average time(s). [Results] In Morris maze, PD model rats compared with the normal control rats, quadrant swimming distance decreased significantly (P < 0.05) and the swimming time in target quadrant was reduced (P < 0.01) significantly; passive avoidance test for multiple testing method, camera lucida observation time percentage (%) was significantly shortened (P < 0.05). [Conclusion] The learning and memory ability of PD rats which were constructed by striatal injection of 6-OHDA was significantly reduced, and it can be used as a model for the study of Parkinson’s disease dementia.