帕金森病模型大鼠学习记忆能力变化的观察
PD Model Rats’ Observation of the Changes of Learning and Memory Ability
DOI: 10.12677/ACM.2016.63025, PDF, HTML, XML, 下载: 1,905  浏览: 2,971  科研立项经费支持
作者: 王硕玥, 王 焱, 方 丽, 孙雅婧, 陈 兵, 邢 华:扬州大学兽医学院,江苏 扬州
关键词: 大鼠帕金森病学习记忆障碍Rats Parkinson Disease Learning and Memory Impairment
摘要: [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。
Abstract: [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.
文章引用:王硕玥, 王焱, 方丽, 孙雅婧, 陈兵, 邢华. 帕金森病模型大鼠学习记忆能力变化的观察[J]. 临床医学进展, 2016, 6(3): 138-146. http://dx.doi.org/10.12677/ACM.2016.63025

参考文献

[1] Jellinger, K.A. (2012) Neurobiology of Cognitive Impairment in Parkinson’s Disease. Expert Review of Neurotherapeutics, 12, 1451-1466.
http://dx.doi.org/10.1586/ern.12.131
[2] Archibald, N.K., Hutton, S.B., Clarke, M.P., et al. (2013) Visual Exploration in Parkinson’s Disease and Parkinson’s Disease Dementia. Brain, 136, 739-750.
[3] 张伟, 杨辉. 6-OHDA制作帕金森病大鼠模型及评估[J]. 四川医学, 2007, 28(8): 818-820.
[4] Paxinos, G. 大鼠脑立体定位图谱[M]. 第3版. 北京: 人民卫生出版社, 2005.
[5] 刘少林, 张均田. 学习记忆方法学[M]. 第3版. 北京: 人民卫生出版社, 2002: 226-834.
[6] Jin, U.-H., et al. (2007) Enhancement of Learning and Memory by a Medicinal Formulation, Saenhyetang, in Mice. Journal of Ethnopharmacology, 109, 271-280.
http://dx.doi.org/10.1016/j.jep.2006.07.030
[7] 瞿融, 马世平, 夏卫军, 等. 定志小丸对不同模型鼠学习记忆功能的影响[J]. 中药药理与临床, 2003, 19(5): 4-6.
[8] 侯悦, 吴春福, 何祥, 等. 氟哌啶醇对小鼠在避暗实验中学习记忆获得、巩固和再现过程的影响[J]. 中国临床康复, 2006, 10(34): 99-102.
[9] Cheng, X.R., Yang, Y., Zhou, W.X., et al. (2011) Expression of VGLUTs Contributes to Degeneration and Acquisition of Learning and Memory. Neurobiology of Learning & Memory, 95, 361-375.
http://dx.doi.org/10.1016/j.nlm.2011.01.010
[10] 吴均. 表达TH、AADC和GCH-I三重基因骨髓基质细胞脑内移植治疗帕金森病模型大鼠的实验研究[D]: [硕士学位论文]. 北京: 首都医科大学, 2014.
[11] 顾平, 张忠霞, 崔冬生, 等. 帕金森病大鼠空间学习记忆和精神行为的改变[J]. 河北医科大学学报, 2010, 31(3): 259-263.
[12] Da, C.C., Angelucci, M.E. and Canteras, N.S. (2002) The Lesion of the Rat Substantia Nigra Pars Compacta Dopaminergic Neurons as a Model for Parkinson’s Disease Memory Disabilities. Cellular & Molecular Neurobiology, 22, 227-237.
http://dx.doi.org/10.1023/A:1020736131907
[13] Braga, R., Kouzmine, I., Canteras, N.S., et al. (2005) Lesion of the Substantia Nigra, Pars Compacta Impairs Delayed Alternation in a Y-Maze in Rats. Experimental Neurology, 192, 134-141.
http://dx.doi.org/10.1016/j.expneurol.2004.11.006
[14] 张贝. 黑质区微注射鱼藤酮对大鼠纹状体和丘脑腹外侧核神经元电活动的影响[D]: [硕士学位论文]. 上海: 华东师范大学, 2007.
[15] 王小川, 张家兴. 帕金森病记忆功能障碍及机制[J]. 中华神经科杂志, 2007, 40(12): 852-856.
[16] Mizoguchi, K., Ishige, A., Takeda, S., et al. (2004) Endogenous Glucocorticoids Are Essential for Maintaining Prefrontal Cortical Cognitive Function. The Official Journal of the Society for Neuroscience, 24, 5492-5499.
http://dx.doi.org/10.1523/JNEUROSCI.0086-04.2004
[17] Brandeis, R., Brandys, Y. and Yehuda, S. (1989) The Use of the Morris Water Maze in the Study of Memory and Learning. International Journal of Neuroscience, 48, 29-69.
http://dx.doi.org/10.3109/00207458909002151
[18] Pearce, J.M., Roberts, A.D.L. and Good, M. (1998) Hippocampal Lesions Disrupt Navigation Based on Cognitive Maps but Not Heading Vectors. Nature, 396, 75-77.
http://dx.doi.org/10.1038/23941
[19] 方松, 余化霖. Morris水迷宫实验中海马相关空间学习记忆的研究进展[J]. 国际病理科学与临床杂志, 2010, 30(4): 321-326.
[20] 王莹, 杨文微, 罗菊花. 避暗实验测定小鼠学习记忆功能方法的研究[J]. 大理学院学报: 综合版, 2011, 10(6): 25-27.
[21] 鲁燕侠, 张癸荣, 聂凌云, 等. 不同实验条件对穿梭箱系统研究大、小鼠学习记忆行为学的影响[J]. 中国药理学通报, 2012, 28(6): 787-791.
[22] 李进, 孙杰, 赵楠, 等. 3种不同脑区定点注射6-OHDA单侧损伤大鼠帕金森病模型的比较研究[J]. 河北医科大学学报, 2016, 37(6): 667-671.