【作者】 钟坚；

【导师】 任惠；

【作者基本信息】 昆明医学院 ， 神经内科， 2011， 硕士

【摘要】 目的：PTPRT主要表达在中枢神经系统中,它可以通过和细胞粘附分子作用来调节突触的形成。当PTPRT过表达时可以增加树突棘的密度,增加抑制性和兴奋性突触的数量。反之,当它被敲除后树突棘的数量则会减少,而兴奋细胞的传递也会减弱。PTPRT的这些功能这提示我们PTPRT可能在癫痫发病中起到了一定的作用,为了验证我们的推测,我们研究PTPRT在难治性颞叶癫痫患者及氯化锂-匹罗卡品(LiCl-PILO)诱导的癫痫动物模型中的表达变化,以探讨PTPRT与癫痫发病机制的关系。方法：从重庆医科大学附属第一医院难治性癫痫脑库中随机抽取30例病人的颞叶脑组织组成实验组和并在重庆医科大学附属第一医院、重庆市第二人民医院因外伤行手术减压患者中获取10例对照颞叶脑组织作为对照组。将重庆医科大学实验动物中心提供6~8周龄健康雄性SD大鼠63只随机分成7个组,其中6组注射氯化-匹罗卡品(LiCl-PILO)诱导癫痫发生,另外1组为对照组；把6组实验组分为发作后6h,1 d,7 d,14 d,30 d,60 d,并取各组颞叶脑组织为研究对象,并与对照组比较。免疫组化,免疫荧光和western blot用于检测PTPRT在人和大鼠脑组织的实验组和对照组的表达及变化规律。结果：在人颞叶皮质中,PTPRT主要在对照组和病例组的神经元有表达,PTPRT在难治性癫痫患者脑组织中比对照组显著升高。在对照组和实验组的大鼠颞叶脑组织中,PTPRT主要在神经元中表达。与对照组相比,PTPRT在颞叶实验组动物中的表达在癫痫发作后24h内是不断升高的,到了一周和两周后表达水平则下降,到了一月和两月后表达又在升高。结论：通过对PTPRT在癫痫动物模型和癫痫病人颞叶脑组织表达规律的研究,结合PTPRT的功能我们推测PTPRT可能通过突触的重构以及苔藓纤维的出芽参与了神经网络的重构,从而导致了难治性癫痫的发生。更多还原

【Abstract】 Objectives:PTPRT is mainly expressed in the central nervous system. PTPRT can regulates synapse formation by interacting with cell adhesion molecules. Overexpressed of PTPRT increased the density of dendritic spines and excitatory and inhibitory synapses. Conversely, knockdown of PTPRT resulted in decrease in the number of dendritic spines and excitatory synaptic transmission. The function of PTPRT indicates it may play a role in the epilepsy. In order to verify our speculation, we investigate the expression changes of the PTPRT in temporal lobe epileptic foci from the experiment animal and epileptic patients and to approach the relationship between PTPRT and epileptogenesis.Methods:We acquired randomly 30 temporal lobe tissue from the brain tissue of intractable epilepsy patients collected by the first affiliated hospital of Chongqing medical college, then acquired 10 temporal lobe tissue from trauma surgery patients which composed the control group. Sixty-three healthy 6-8 years SD rats provided by the experimental animal center of Chongqing university were divided to seven groups, six groups were injected lithium -pilocarpine and obtained epilepsy, the other one was control group. The six experiment groups respectively contained 9 rats at 6h,1d,7d,14d,30d,60d days post-seizure. We get the epilepsy lobe tissue from the experiment and control groups as research objects, using the immunohistochemistry, immunofluorescence and Western blot analysis to assess the expression of PTPRT and its changes.Results:In the temporal lobe tissue of intractable patients and control groups, PTPRT was mainly expressed in the neurons. PTPRT significantly increased in intractable epilepsy patients than the control group. PTPRT was mainly expressed in the neurons in the temporal lobe brain tissue of the rats in the control group and experiment groups. Compared with control groups, PTPRT expression in the temporal lobe tissue was rising within 24h post-seizure, and decreased 1 and 2 weeks post-seizure, then it is on the rise 1 and 2 months post-seizure.Conlusions:Through researches on the PTPRT expression in the temporal lobe brain tissue in the intractable epilepsy patients and animal models, together with the function of PTPRT, we presume that the PTPRT play a role in the synapses reorganization and moss fiber sprouting, participating in the reconstruction of the neural network which led to the intractable epilepsy.更多还原