目的 研究甘氨酸转运体1(GlyT1)抑制剂M22 对戊四氮(PTZ)诱导的癫痫小鼠认知功能障碍的改善作用.方法 按照体质量随机将筛选的50 只C57BL/6 小鼠分为3组:空白对照组(Control,n = 10),模型组(Model,n = 20), M22 组(M22,n = 20).空白对照组腹腔注射等量的生理盐水,模型组和M22 组小鼠腹腔注射PTZ (30 mg /kg) 制备慢性点燃癫痫模型,连续腹腔注射PTZ 2 周时间,并同时通过灌胃给予M22 组小鼠40 mg /(kg·d) 的M22.2 周后采用 Morris 水迷宫实验对其学习记忆功能进行评价,然后将小鼠处死,对其海马进行HE 染色,并测定小鼠大脑皮层的凋亡相关蛋白,对其神经元细胞的凋亡情况进行评价.结果 Morris 水迷宫实验结果显示癫痫发作导致了小鼠认知功能障碍,而M22 对其认知障碍具有改善作用;HE 染色结果显示模型组小鼠神经元明显发生凋亡,而M22 具有保护作用.凋亡相关蛋白测定显示M22 对于癫痫导致的神经元凋亡具有显著的保护作用.结论 甘氨酸转运体1 抑制剂M22 能够显著提高癫痫小鼠的学习、记忆能力,抑制神经元细胞凋亡,为癫痫或者难治性癫痫患者提供新的选择.%Objective To study the effects of glycine transporter 1 (GlyT1) inhibitor M22 on cognitive impairment in epileptic mice induced by amyl four nitrogen. Methods According to the weight,50 C57BL /6 mice were randomly divided into three groups: blank control group (Control,n = 10),model group (Model,n = 20),M22 group (M22,n = 20). Chronic ignited epilepsy model were prepared by intraperitoneal injection of PTZ (30 mg / kg) in model group and M22 mice,while the control group was injected saline,continuous intraperitoneal injection of four nitrogen for 2 weeks and at the same time by intragastric administration of M22 mice 40 mg /(kg·d) M22. After two weeks,the learning and memory function was evaluated by Morris water maze test. Then the mice were sacrificed and their hippocampus were stained with HE stainning,and the apoptosis related proteins in the cerebral cortex of mice were measured,and the apoptosis of neurons was evaluated. Results The results of Morris water maze test showed that epileptic seizures induced cognitive impairment in mice,while M22 could improve their cognitive impairment. HE staining showed that neurons in the model group were obviously apoptosis,while M22 exerted protective effect. Apoptosis related protein assay showed that M22 had a significant protective effect on the neuronal apoptosis induced by epilepsy. Conclusion Glycine transporter 1 inhibitor M22 can significantly improve the learning and memory ability of epileptic mice,inhibit neuronal apoptosis,and provide new options for patients with epilepsy or intractable epilepsy.
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