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癫痫大鼠空间学习—记忆行为学及扣带回脑区c-jun和GABA免疫反应活性变化

论文标题:癫痫大鼠空间学习—记忆行为学及扣带回脑区c-jun和GABA免疫反应活性变化
The Changes of Epileptic Rat"s Spatial Learning Memory Ethology and Immunoreactivity of C-Jun and GABA in Cingulate Gyrus
论文作者
论文导师 赵杰,论文学位 硕士,论文专业 神经病学
论文单位 大连医科大学,点击次数 75,论文页数 43页File Size1956K
2007-05-01论文网 http://www.lw23.com/lunwen_1012589527/
epilepsy ;spatial memory; cingulate gyrus ;GABA ;c-jun
背景:癫痫是常见的中枢神经系统疾病之一,反复自发发作是其主要特点。其所造成的认知功能障碍给病人及其家属带来了极大的痛苦。以往对于癫痫学习记忆障碍的研究主要集中在海马上,并且肯定了海马与癫痫学习记忆障碍之间的相关性,对于扣带回的研究却相对较少。由于扣带回与海马毗邻并且有着广泛的纤维联系,并且许多研究也指出扣带会在动物学习记忆的形成和癫痫的发病上都有着其重要地位,所以癫痫所造成的学习记忆障碍与扣带回脑区是否具有相关性就成为一个值得进一步探讨的问题,这个问题的明确将会促进我们对癫痫所致学习记忆障碍的认识,并且可以对癫痫病人的治疗提供新的思路。 目的:观察海仁酸癫痫模型制作过程中癫痫大鼠的行为学变化特点;用Morris水迷宫实验观察各处理组大鼠空间学习-记忆行为学特点;运用免疫组织化学方法观察癫痫大鼠扣带回脑区c-jun, GABA免疫反应活性变化,探讨扣带回与癫痫大鼠空间学习记忆障碍之间的可能关系。 方法:实验采用成年雄性健康SD大鼠制作海仁酸(Kainic acid, KA )癫痫模型,进一步采用蝎毒制作癫痫持续状态后未形成难治性癫痫大鼠组;运用Morris水迷宫DMS-2系统观察各组大鼠的空间学习记忆行为学变化,通过免疫组织化学实验观察各组大鼠扣带回脑区GABA和c-jun的免疫反应活性变化;采用HPIAS系列彩色病理图文分析系统对GABA、c-jun免疫阳性细胞进行定量计数;实验结果采用SPSS11.5软件进行统计处理。 结果: 50只SD大鼠经过KA造模和蝎毒处理,有7只大鼠成为未形成难治性癫痫的癫痫大鼠,12只大鼠成为难治性癫痫大鼠;水迷宫实验中难治性癫痫组大鼠与空白对照组相比表现出了明显降低的空间学习记忆能力,未形成难治性癫痫组大鼠与空白对照组相比其空间学习记忆未见明显改变;免疫组织化学实验中难治性癫痫组大鼠扣带回脑区与空白对照组和未形成难治性癫痫大鼠组相比GABA和c-jun免疫活性明显降低,未形成难治性癫痫大鼠组扣带回脑区GABA和c-jun免疫活性与空白对照组相比未见明显改变。并且在各组大鼠扣带回脑区GABA和c-jun的免疫活性存在明显的正相关性。 结论:癫痫大鼠出现学习记忆障碍的关键因素是其是否发展成为难治性癫痫;难治性癫痫大鼠扣带回脑区脑区的GABA、c-jun免疫反应性明显降低并且两者之间的变化有明显的相关性;难治性癫痫所致的空间学习记忆障碍与动物扣带回脑区GABA能神经元的损伤有关。
Background: Epilepsy is common disease of central nervous system. Its principle feature is repeating seizures. The cognitive disturbance that epilepsy results in has brought great suffering to the patients and his family. In the past, the investigation about the cognitive disturbance of epilepsy had been mainly on the hippocampus. However, the investigation on cingulate gyrus was relatively less. Account of the important position of cingulate gyrus on the formation of memory and seizure of epilepsy, it is deserved to investigate the correlation between cingulate gyrus and the cognitive disturbance of epilepsy. Identifying this problem will improve our knowledge about the cognitive disturbance of epilepsy and provide a new way to treat epilepsy patients. Objective: To observe the ethology features of epilepsy rat during the model building of epilepsy; To observe the ethology features of spatial learning memory that epilepsy rat emerges in the Morris Water Maze; To investigate the immunoreactivity of C-Jun and GABA in the cingulate gyrus and the correlation between the cingulate gyrus and the epilepsy rat’s spatial learning memory. Method: In this experience, we applied healthy male adult Sprague-Dawley(SD) white rats to make epilepsy models by injecting kainic acid and to make epilepsy models that are not intractable by using kainic acid in cooperation with scorpion venom. We observed the changes of animal models’spatial learning memory by the Morris Water Maze and theimmunoreactivity of GABA and c-jun in the cingulate gyrus by immunohistochemistry. Results: (1) 50 SD rats were used to make animal models, among them, 12 became intractable epilepsy model and 7 became epilepsy model that are not intractable; (2) Compared with the blank, intractable epilepsy model appeared obviously decreased spatial learning memory in Morris Water Maze, however, epilepsy models that are not intractable appeared no obvious differences; (3) The immunoreactivity of GABA and c-jun in the cingulate gyrus of intractable epilepsy model was decreased obviously compared with the blank. However, the epilepsy model that are not intractable appear no obvious differences. Moreover, in the cingulate gyrus, there was an obvious correlation on immunoreactivity between GABA and c-jun. Conclusion: (1) The key point of epilepsy rat’s spatial learning memory impairment is if the epilepsy have become to intractable epilepsy; (2) The immunoreactivity of GABA and c-jun in cingulate gyrus of intractable epilepsy rat decreases obviously and there is an obvious correlation on the changes of immunoreactivity between GABA and c-jun; (3) The impairment of spatial learning memory that intractable epilepsy results in is correlated to the damage of GABA energy neuron in cingulate gyrus.

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