慢性不可预知温和应激配合孤养抑郁模型大鼠海马的代谢组学研究  

Hippocampus Metabonomic Study Using a CUMS Rat Model of Depression

作　　者：郭秉荣[1,2] 杨岚[1,2] 刘佳丽[1,2] 秦雪梅[1] 高晓霞[1] 

机构地区：[1]山西大学中医药现代研究中心,太原030006 [2]山西大学化学化工学院,太原030006

出　　处：《中国药学杂志》2013年第14期1160-1164,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(81001688);国际科技合作项目(2011DFA32630);"重大新药创制"科技重大专项(2012ZX09103201-035);山西省基础研究青年科技研究基金(2011021007-1);山西省高等学校中青年拔尖创新人才支持计划资助

摘　　要：目的采用GC-MS代谢组学技术分析慢性不可预知温和应激配合孤养抑郁大鼠的海马组织,寻找海马中与抑郁症相关的代谢产物,为阐明抑郁症发病机制提供依据。方法采用慢性不可预知温和应激配合孤养进行造模,以大鼠体重,糖水偏爱实验和旷场实验评定大鼠行为学的变化,同时采集海马组织进行GC-MS代谢组学分析并寻找生物标志物。结果行为学数据显示,与空白组相比,模型组大鼠的体重显著降低(P<0.05),糖水偏爱率显著降低(P<0.05),在旷场实验中模型组大鼠的穿格数和直立次数显著降低(P<0.05),显示了抑郁状态。代谢组学分析结果显示,散点图中空白组与模型组明显以T1轴分开,通过载荷图寻找出了慢性不可预知温和应激配合孤养抑郁模型大鼠海马组织中谷氨酸(Glu)、天冬氨酸(Asp)、甘氨酸(Gly)、γ-氨基丁酸(GABA)、N-乙酰天门冬氨酸(NAA)等10种潜在生物标志物。结论运用GC-MS代谢组学技术分析慢性不可预知温和应激配合孤养抑郁模型大鼠的海马,寻找到了海马中与抑郁症相关的代谢产物,说明抑郁症的发病机制与能量代谢、氨基酸代谢和脂代谢相关。ObjectiveTo analysis the regulation of biomarkers by an metabonomic investigation of chronic unpredictable mild stress （CUMS） rats. To provide a clue for elucidate the mechanism of depression. Methods CUMS induced rat animal depression model, the behavioral changes of rats were observed; meanwhile, hippocampus samples were obtained and subjected to GC-MS analysis to find potential biomarkers of depression. Results Body weight, sucrose intake in the sucrose preference , ambulationn number and rearing number in open-field test of the CUMS rats decreased significantly after 21 d compared with those of the control groups. Metabonomics analysis showed that the model group separated the control group from T1. Ten potential biomarkers are identified from the loading plot between control and model group. Conclusion Ten biomarkers are identified among the detected compounds. These Results suggest that the depressed state may be associated with perturbation of amino acid metabolism, energy metabolism and lipid metabolism.

关 键 词：慢性不可预知温和应激 GC-MS代谢组学技术分析 海马 代谢组学 

分 类 号：R965[医药卫生—药理学]