中文摘要：

目的：研究发育期大鼠慢性内侧颞叶癫痫（mesial temporal lobe epilepsy，MTLE）模型潜伏期末海马的形态学以及蛋白表达谱变化，揭示慢性MTLE发病机制。方法：建立氯化锂-匹罗卡品诱导的发育期大鼠MTLE模型，取致痫后3周末的对照组（n=20）和MTLE模型组（n=20）大鼠为研究对象，尼氏及Timm染色观察海马神经元丢失和苔藓纤维出芽情况；采用二维凝胶电泳（two dimensional gel electrophoresis，2-DE）结合质谱分析对两组间的差异表达蛋白质进行鉴定；Western印迹对部分差异表达蛋白进行印证。结果：MTLE模型组海马内可见明显的海马神经元丢失和苔藓纤维出芽；建立了发育期大鼠慢性MTLE模型潜伏期末的海马蛋白质2-DE图谱，共鉴定了差异表达蛋白质31个，分别属于神经递质和突触发生相关的蛋白、细胞骨架蛋白、细胞连接蛋白、能量代谢和线粒体功能蛋白、生物活性酶类、细胞结构相关蛋白质以及信号转导相关蛋白质等；Western印迹对部分蛋白水平检测的结果与蛋白质组学结果一致。结论：Dynamin-1，neurogranin和ubiquitin等一系列突触相关的蛋白表达异常，可导致突触重构、异常苔藓纤维增生和异常神经兴奋环路的形成，是MTLE发病机制中至关重要的环节。

英文摘要：

Objective： To examine the changes of morphology and differentially expressed proteins in hippocampus at the latent stage of chronic mesial temporal lobe epilepsy （MTLE） in immature rats, and to explore the global mechanism of chronic MTLE at a new point.Methods： MTLE models of immature rats were induced by lithium-pilocarpine. The rats were divided into 2 groups randomly： a control group （n=20） and an MTLE model group （n=20）. At the latent stage, nissl and Timm staining were performed to evaluate the cell loss and mossy fiber sprouting. The differentially expressed proteins were separated by 2-dimensional polyacrylamide gel electrophoresis （2-DE） combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS） technology. Western blot was used to determine the differentially expression levels of partial proteins. Results： Neuron loss and abnormal mossy fiber sprouting were obviously observed in the hippocampus in the MTLE model group; 2-DE patterns of hippocampus of the MTLE model group in latent stage and the control group were established. Thirty-one differential proteins were identified by MALDI-TOF-MS, which were categorized into several groups by biological functions： synaptic and neurotransmitter release related proteins, cytoskeletal proteins, cell junctions proteins, energy metabolism and mitochondrial proteins, biological enzymes, cellular structure related proteins~ signal regulating molecular and others. The expression levels of partial proteins determined by Western blot were similar to the changes ofproteomics. Conclusion： The differentially expressed proteins of synapse-related proteins such as dynamin-1, neurogranin and ubiquitinj which cause the synapse reorganization and mossy fiber terminal sprouting related to the formation of abnormal excitatory network, probably play critic roles in the mechanism of MTLE.