氟西汀作用于慢性温和不可预见性应激大鼠海马组织前后的差异蛋白质组学研究

目的:采用蛋白组学方法研究氟西汀对慢性温和不可预见性应激(chronic unpredictable mild stress,CUMS)大鼠海马组织蛋白质表达的影响,以探讨氟西汀抗抑郁的作用机制。方法:采用CUMS建立大鼠抑郁模型。造模完成后,氟西汀组给予氟西汀(3 mg/kg)灌胃给药,每天1次,连续21 d。行为学实验检测大鼠抑郁行为的变化。提取的大鼠海马组织蛋白质样品经同位素标记相对和绝对定量标记、强阳离子柱分离、反相液相色谱分离、质谱分析,获取的串联质谱数据通过Protein.pilot 3.0软件鉴定蛋白质,运用生物信息学分析差异表达的蛋白质功能。结果:共鉴定出5 109个蛋白质,41个差异表达的蛋白质,其中36个蛋白质表达上调,5个蛋白质表达下调,涉及氧化还原、信号传导、合成代谢、对外界刺激压力的反应等过程。结论:同时筛选到了四个可能与氟西汀抗抑郁作用密切相关的差异蛋白,分别是Neuronal calcium sensor 1(NCS-1)、Receptor-type tyrosine-protein phosphatase zeta、Neurocan core protein和Sodium-and chloride-dependent GABA transporter,但这些蛋白在抑郁症的发生、发展过程中的作用尚未完全清楚,需进一步深入研究。

Proteomics study of effects of fluoxetine on expression of proteins in hippo-campus tissues of CUMS rats

Objective:The effects of fluoxetine on expression of proteins in hippocampus tissues of chronic unpredicted mild stress(CUMS)rats by proteomics study were studied to explore the anti-depression mechanism.Methods:CUMC was taken to establish rat depression model.Rats in fluoxetine group were administrated with fluoxetine (3 mg·kg -1 ·d -1 )after stress procedure for 21 day .The extractd proteins from hippocampus tissues were digested by equal amount of trypsin and identified by ITRAQ coupled with the cation column and LC-MS /MS technology and then analyzed by Protein Pilot 3.0 search engine.Using bioinformatics to analyze differ-entially expressed proteins.Results:A total of 5 109 proteins were identified,including 41 significantly differentially expressed proteins, which 5 proteins were down-regulated and 36 were up-regulated and involves redox reactions,signal transduction,anabolic metabolism, pressure to external stimuli of reaction process.Conclusion:Screening to four possible with fluoxetine antidepressant effect is closely re-lated to the differences in protein,respectively is Neuronal calcium sensor 1 (NCS-1 ),Receptor-type tyrosine-protein phosphatase zeta, Neurocan core protein and Sodium-and chloride-dependent GABA transporter,but these proteins in the role in the process of the occur-rence and development of depression is still not clear and need further study.