发育期大鼠内侧颞叶癫痫模型丙戊酸治疗前后的蛋白质组学研究

Comparative proteomic analysis of differentially expressed proteins in hippocampus of developmental rats with mesial temporal lobe epilepsy following treatment with valproate

目的研究丙戊酸(VPA)对发育期大鼠内侧颞叶癫痫(MTLE)模型海马蛋白质表达谱的影响,寻求与VPA抗癫痫作用相关的蛋白质以及探讨VPA在MTLE发病早期发挥抗癫痫作用的机制。方法建立氯化锂-匹罗卡品诱导的发育期大鼠MTLE模型,采用二维凝胶电泳(2-DE)技术分离海马总蛋白,PDQuest软件识别差异表达蛋白质,基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)进行鉴定。结果建立了VPA治疗前后的MTLE模型大鼠海马蛋白质的2-DE图谱。质谱鉴定出9个差异表达的蛋白质,其中4个在VPA治疗后表达上调;5个下调。结论本实验成功建立了发育期大鼠MTLE模型VPA处理前后的海马蛋白质2-DE图谱;β-synuclein、Neurogranin等差异表达蛋白可能与VPA在MTLE发病早期发挥抗癫痫作用的机制相关。

Objective To investigate the effects of valproate （VPA） on the protein expression profile in hippocampus of developmental rats with mesial temporal lobe epilepsy （MTLE）, then to explore the anti-epileptic relating proteins of VPA and to approach the mechanism of which VPA treated in early stage of the MTLE developing.Methods The MTLE models of developmental rats were induced by lithium-pilocarpine.Proteins in the hippocampus were separated by two-dimensional polyacrylamide gel electrophoresis （2-DE） technology. PDQuest software was used to analyze 2-DE images,and MALDI-TOF-MS was used to identify the differentially expressed proteins.Results The 2-DE patterns of VPA treated and untreated MTLE rat hippocampi were established. 9 differential proteins were identified by MALDI-TOF-MS,of which 4 proteins were up-regulated and 5 proteins down-regulated after VPA treated.Conclusion The 2-DE profiles of hippocampus proteome in developmental rats with VPA treated and untreated MTLE were established in this study.The differentially expressed proteins such as β-synuclein and Neurogranin may be related to the anti-epileptic mechanism of VPA which was used in the early stage of the MTLE developing.