中文摘要：

目的研究兴奋性氨基酸转运体2（EAAT2）过表达对癫痫发作及SE诱导的海马神经元死亡的作用。方法实验采用野生型或者EAAT2转基因FVB／N小鼠，腹腔注射匹鲁卡品诱导癫痫持续状态（SE）。SE后3d，取脑、固定、切片，进行EAAT2、生长抑素的免疫组化染色以及甲酚紫染色，分别对海马CA1和齿状回门区阳性神经元进行计数。结果与野生型动物相比，EAAT2在转基因小鼠海马中表达显著增加。野生型小鼠达到SE或者死亡所需的总匹鲁卡品剂量为344±40．3mg／kg，而EAAT2转基因小鼠达到同等效应所需剂量为657±119．9mg／kg，显著高于野生型所用剂量（P〈0．05）。SE后3d，野生型小鼠海马CA1区锥体细胞层神经元相对数量为0．56，而转基因动物中为0．9，显著高于野生型动物（P〈0．05）。同时，野生型和转基因小鼠癫痫后齿状回门区中间神经元相对数量分别为0．11和0．67，转基因组数量显著高于野生型组（P〈0．05）。野生型小鼠癫痫后齿状回门区生长抑素阳性神经元数量为0，但是，在EAAT2转基因小鼠，数量为0．4，显著高于野生型（P〈0．05）。结论EAAT2过表达对SE产生及其诱导的神经元死亡具有显著保护作用。过表达的EAAT2可能通过加强细胞外谷氨酸转运而调控其兴奋毒性。

英文摘要：

Objective The purpose of this experiment is to study the effect of excitatory amino acid transporter 2（EAAT2） over expression on status epileptics （SE） and SE-induced neuronal death. Methods The meuse SE models were established by intraperitoneal injection of pilocarpine on EAAT2 transgenic mice and wild- type mice. Three days after SE, brains were harvested and cut into 40 m sections. EAAT2 level was determined by immunostaining. Survived neurons were detected by cresyl violet staining. Somatostatin-positive neurons were also detected by immunostaining. Cell numbers in hippocampal CA1 and hilus of dentate gyrus were counted and compared between the transgenic and wild-type animals. Results Compared with the wild-type animals, EAAT2 was over-expressed in the transgenic mice. A significant larger dose of pilocarpine was needed to induce SE in EAAT2 transgenic mice, compared with the dose for the wild-type animals （657 ±119.9 mg/kg, n =4 vs 344 ± 40.3 mg/kg, n =4; P〈0.05）. Three days after SE, the relative pyramidal cell number in CA1 was 0.56 in the wild-type mice, while the relative cell number was 0. 9 in the EAAT2 transgenic animals. The post-SE cell number in the hippocampus CA1 pyramidal layer was higher in the EAAT2 transgenic mice than that in the wild- type animals. In the DG hilus, the relative post-SE cell numbers were 0. 11 and 0. 67 in the wild-type animals and EAAT2 transgenic mice, respectively. In the wild-type animals, the relative number of somatostain-positive cells was 0 in the DG hilus after SE. However, the number was 0.4 in the EAAT2 transgenic mice. Condusion Our results indicate that over-expressed EAAT2 has significant protective effect on SE and SE-induced neuronal death. Over-expressed EAAT2 may modulate the excitotoxity during seizure by enhancing extracellular glutamate uptake.