难治性癫痫大鼠海马线粒体蛋白质的差异表达

目的 建立难治性癫痫大鼠模型，通过对海马线粒体蛋白质组的研究，探讨其发病机制并寻找新的治疗靶点。方法 应用固相pH梯度等电聚焦和十二烷基硫酸钠－聚丙烯酰胺凝胶电泳（SDS PAGE）二维电泳，基质辅助激光解析/电离-飞行时间质谱（MALDI TOF）技术分析和鉴定耐药/非耐药癫痫大鼠海马线粒体差异蛋白。结果 耐药组癫痫大鼠海马线粒体19种蛋白表达异常，5种表达上调的蛋白为3-磷酸甘油醛脱氢酶、磷酸丙糖-1、电压依赖性阴离子通道1、醛糖A和微管蛋白，14种表达下调的蛋白质为顺乌头酸酶、谷氨酸脱氢酶、苹果酸脱氢酶、NADH脱氢酶、ATP合成酶、丙酮酸激酶同工酶类似物、ATP结合盒B亚家族、磷脂酶A2、丝氨酸蛋白酶抑制剂、热休克蛋白、解偶联蛋白、Cofilin 1、醛脱氢酶和电压依赖性阴离子通道2。结论 难治性癫痫大鼠海马线粒体存在大量差异表达蛋白，可能参与癫痫耐药的发生。

Differential expressions of the mitochondrial proteome in the hippocampus of pharmaco-resistant epileptic rats

Objective    To explore the pathogenesis mechanism and the potential therapeutic targets of intractable epilepsy through the technique of mitochondrial proteomics in pharmacoresistant epileptic models. Methods    Expression profiles of mitochondrial proteins in pharmaco resistant rats and non-pharmaco-resistant rats were compared and analyzed by using immobilized pH gradient, SDS-PAGE and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). Results    All 19 protein spots were differentially expressed when compared with non-pharmaco-resistant epileptic rats. 5 up-regulated proteins in pharmaco-resistant epileptic hippocampal mitochondria were glyceraldehydes-3-phosphate dehydrogenase, triosephosphate isomerase-1, voltage-dependent anion channel 1, aldose A, and tubulin beta 2. 14 down-regulated proteins in pharmacoresistant epileptic hippocampal mitochondria were aconitase, glutamate dehydrogenase 1, malate dehydrogenase, NADH dehydrogenase 1 alpha subcomplex 10, ATP synthase alpha subunit precursor, similar to pyruvate kinase isoenzyme, ATP binding cassette, subfamily B, member 10, phospholipase A2, serine proteinase inhibitor， serpin, heat shock protein 70, uncoupling protein, cofilin 1, aldehyde dehydrogenase, and voltage-dependent anion channel 2. Conclusion    Many mitochondrial proteins are differentially expressed, which are perhaps involved in the pathogenesis of intractable epilepsy.