抑郁模型大鼠小脑的比较蛋白组学初步研究

Preliminary study on the comparative proteomics of the cerebellum of the rat depression model

目的通过抑郁模型大鼠小脑的差异蛋白组学分析，探讨小脑在抑郁症病理生理过程中的作用。方法建立慢性不可预见性温和应激（CUMS）抑郁大鼠模型，并应用同位素标记相对和绝对定量技术结合多维液相色谱-串联质谱分析CUMS组和对照组大鼠小脑差异蛋白质。随后对结果采用DAVID生物信息数据库进行分析。结果与对照组大鼠比较，CUMS组大鼠糖水偏好值明显降低，差异有统计学意义（P＜0.05）。对两组样品鉴定，共得到差异蛋白55个，其中在CUMS组中表达下调的有18个，表达上调的有37个。这些蛋白主要参与神经递质代谢、糖酵解、ATP合成利用、脂质代谢、氨基酸代谢等生物过程。结论本研究所发现的差异蛋白可能是抑郁症小脑功能异常的神经生物学基础，对深入探讨小脑在抑郁症发病机制中的作用提供了重要的线索。

Objective To explore the role of cerebellum in the pathogenesis of depression, by ana- lyzing the differently expressed proteins in the cerebellum of the rat depression model.Methods Chronic unpredictable mild stress （CUMS） rat depression model was conducted. Different cerebellum protein lev- els between CUMS and control rats were examined using a multi-dimensional liquid chromatography- tandem mass spectrometry. The results were further analyzed with DAVID database. Results The CUMS rats showed decreased sucrose preference compared with the control rats （P 〈0.05）. Among the 55 cerebellum proteins expressed differently between the CUMS and control rats, 18 were down-regu- lated and 37 were up-regulated in the CUMS rats as compared with the control rats. These proteins were mainly associated with neurotransmitter metabolism, glycolysis, ATP metabolism, lipid metabo- lism, and amino acid metabolism.Conclusions The differentially expressed proteins found in this study may be the basis of the biological basis of depression, and provide important clues for the further study of the cerebellum role in the pathogenesis of depression.