基于核磁共振的代谢组学方法对CUMS动物模型的初步研究

Preliminary studies of the CUMS animal models with metabonomics based nuclear magnetic resonance

目的利用基于磁共振的代谢组学方法对CUMS大鼠动物模型进行研究,分析其脑内代谢物质的变化特点,与临床抑郁症患者的磁共振波谱研究结果对照,从代谢角度对CUMS动物模型进行初步评价。方法 Wistar大鼠12只,分为对照组和模型组,模型组建立CUMS模型后断头取脑,取出两侧海马及额叶脑组织。采用基于核磁共振技术的代谢组学方法分析对照组与模型组脑内不同部位的代谢物变化特点,并分别计算NAA/Cr、Glu/Cr、Cho/Cr、MI/Cr值。结果对照组与模型组分别处于PCA图中不同区域,可以区分正常和抑郁状态大鼠;对照组与模型组的右海马、右额叶PCA特征值差异明显。与对照组大鼠比较,模型组右海马、右额叶NAA/Cr值和MI/Cr值明显减低、Glu/Cr值明显升高;右额叶Cho/Cr值明显升高。结论 CUMS抑郁模型能够模拟抑郁症患者脑内部分神经生化的变化情况。以代谢组学方法评价抑郁症动物模型提供了一种从神经生化角度评价动物模型的新思路。

Objective To analyse the neurochemical alterations in depressed rats by using metabonomics based MR （nu- clear magnetic resonance）, the aim was to discuss whether the chronic unpredictable mild stress （CUMS） models could im- itate some metabolic changes in depressed patients. Methods Twelve Wistar rats that were divided into model group and control group. Six rats in model group were established into CUMS models. Left and right hippocampus and frontal lobe were taken out and made into white crystal powder after several processing. 1 H-MRS was performed by using a NMR scanner. Metabonomics analysis was performed by using PCA. NAA/Cr, Glu/Cr, Cho/Cr and mI/Cr were calculated re- spectively. Results Metabolic characteristics of model group and control group were in different areas of the PCA map of metabonomics. There were statistical metabolic differences in right hippocampus and frontal lobe between the two rat groups. The right hippocampus and right frontal lobe in model rats showed significantly lower NAA/Cr, MI/Cr levels, and higher Glu/Cr levels, the right frontal lobe revealed increased Cho/Cr levels. Conclusion CUMS animal model can imitate some metabolic changes in depressed person. The application of metabonomics provides a more reasonable way in e- valuating depression animal model than only with behavior data.