基于代谢组学技术的宁神灵抗抑郁作用机制研究＊

目的 采用代谢组学技术研究宁神灵抗抑郁的作用机制，确定抑郁症的生物标记物及宁神灵药效作用的关键通路。方法 参考Banasr的CUMS模型建立方法制备抑郁症大鼠模型。采用超高效液相-高分辨串联质谱（AB TripleTOF 5600⁺LC/MS/MS）系统分析抑郁症大鼠尿液代谢物含量及组成的变化，聚焦抑郁症核心生物标记物及关键代谢酶，并评价宁神灵抗抑郁的作用机制。结果 通过模式识别分析发现，抑郁症大鼠代谢发生显著差异代谢，其代谢轮廓在健康状态区域发生显著偏移。对影响代谢分布的生物标记物分析发现，主要涉及苯丙氨酸、酪氨酸、赖氨酸、甘氨酸、谷氨酰胺、组氨酸脯氨酸、泛酸、二羟基丙酮磷酸盐、3-羟基丁酸、肌酐、腺苷。其主要涉及氨基酰基-tRNA生物合成、氮代谢、硫胺素代谢、苯丙氨酸、酪氨酸和色氨酸生物合成等，给予宁神灵后其含量呈回调趋势。结论 宁神灵对抑郁症有很好的治疗作用，宁神灵可能通过氨基酸代谢、糖酵解、TCA循环和ATP生物合成过程中调节发挥抗抑郁的治疗作用。

Mechanism of Ningshen Ling s antidepressant effect based on metabolomics

Objective To study the antidepressant mechanism of Ningshen Ling by metabolomics, and to determine the biomarkers of depression and the key pathway of Ningshen Ling. Methods The depression model of rats was prepared with reference to Banasr s CUMS model. Ultra-high performance liquid chromatography-high resolution tandem mass spectrometry (AB TripleTOF 5600⁺LC/MS/MS) was used to analyze the changes of urinary metabolites in depressive rats, focusing on the core biomarkers and key metabolic enzymes of depression, and to evaluate the antidepressant mechanism of Ningshen Ling. Results By pattern recognition analysis, we found that the metabolism of depressive rats was significantly different, and the metabolic profile of depressive rats was significantly deviated in the healthy region. Biomarkers affecting metabolic distribution were found to be mainly involved in phenylalanine, tyrosine, lysine, glycine, glutamine, Histidinyl-Proline, pantothenic acid, dihydroxy pyruvate phosphate, 3-hydroxybutyric acid, creatinine, adenosine. It mainly involves aminoacyl-tRNA biosynthesis, nitrogen metabolism, thiamine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Conclusion Ningshen Ling has a good therapeutic effect on depression. Ningshen Ling may play an antidepressant role through the regulation of amino acid metabolism, glycolysis, TCA circulation and ATP biosynthesis.