目的 采用¹H-NMR代谢组学技术研究慢性温和不可预知应激（CUMS）抑郁模型大鼠粪便中内源性代谢产物的变化规律，寻找潜在的生物标志物。方法 大鼠分成模型组与对照组。采用CUMS程序对模型组大鼠进行为期4周的造模，造模结束后收集大鼠粪便。应用¹H-NMR技术及多元统计分析方法分析大鼠粪便提取物中内源性代谢产物的变化规律。结果 模型组与对照组大鼠的行为学指标差别明显，表明CUMS大鼠抑郁模型复制成功。在大鼠粪便的¹H-NMR图谱中可以指认出30种内源性代谢产物，模型组中谷氨酰胺、乳酸、天冬氨酸的量明显增加，而尿嘧啶、酪氨酸、苯丙氨酸的量明显降低，且与对照组相比差异显著（P＜0.05、0.01）。结论 通过研究CUMS抑郁模型大鼠粪便中内源性代谢产物的变化规律，阐明与抑郁症有关的潜在生物标志物，为抑郁症的发病机制及临床诊断研究提供实验依据。

Objective To obtain the potential biomarkers of chronic unpredictable mild stress (CUMS) rats, the change of endogenous metabolites in the faeces of CUMS rats was analyzed using ¹H-NMR coupled with metabonomics. Methods CUMS procedure was conducted for four weeks, CUMS rat model was duplicated, and the faeces of rats was collected at the end of the procedure. The change of endogenous metabolites in faeces was analyzed using ¹H-NMR coupled with multivariate statistical analysis. Results The PLS-DA scores plot demonstrated that behavior indexes of rats in the control group were significantly different from these of rats in CUMS group, suggesting the CUMS model of depression in rats was prepared successfully. Thirty metabolites were identified in the ¹H-NMR spectra of faeces, the concentration of glutamine, lactate, and aspartate was increased while that of β-glucose, uracil, tyrosine, and phenylalanine was decreased in CUMS model group with the significant difference compared with the control group (P < 0.05, 0.01). Conclusion By researching the change of endogenous metabolites in the faeces of CUMS rats, the potential biomarkers in the faeces of CUMS rats are picked up to lay the foundation for the study on the depression pathogenesis and clinical diagnosis.

国家自然科学基金资助项目（81173366，81102833）；山西省基础研究项目（2012021031-2）；国家“重大新药创制”科技重大专项课题（2012ZX09103201-035）；国家国际科技合作计划项目（2011DFA32630）