基于^(1) H-NMR肝脏代谢组学的白芍抗抑郁作用研究

Study on Antidepressant Effect of Radix Paeoniae AlbaBased on ^(1)H-NMR Hepatic Metabolomics

目的:分析白芍对慢性不可预知温和应激抑郁(CUMS)大鼠肝脏内源性代谢物的调控作用,阐明白芍抗抑郁相关的代谢通路。方法:大鼠被随机分为空白对照组、CUMS模型组、文拉法辛组和白芍高、低剂量组,通过抑郁症的行为学指标评价白芍药效,利用1H-NMR代谢组学技术,结合多元统计分析方法,筛选与抑郁相关的差异代谢物,分析给予大鼠白芍高、低剂量后肝脏内源性代谢物的变化情况,并进行代谢通路分析。结果:与空白组大鼠比较,模型组大鼠行为学指标均有显著变化,即体质量、旷场穿越格数、直立次数、糖水偏爱率降低(P<0.001),强迫游泳不动时间增加(P<0.001);^(1)H-NMR代谢组学结果表明,CUMS组影响24种代谢物和10条代谢通路发生变化,白芍能显著回调全部的差异代谢物并且通过影响全部的代谢通路发挥抗抑郁作用,包括:D-谷氨酰胺和D-谷氨酸代谢;谷胱甘肽代谢;甘氨酸代谢等。结论:白芍能够改善大鼠CUMS模型的抑郁样行为、调节肝脏内源性代谢物变化,其机制可能与调节D-谷氨酰胺、D-谷氨酸、谷胱甘肽代谢等相关代谢通路有关。

Objective:To analyze the regulatory effect of Radix Paeoniae Alba on hepatic endogenous metabolites in rats with chronic unpredictable mild stress(CUMS)-induced depression,thus to clarify the metabolic pathways related to the antidepressant effect of Radix Paeoniae Alba.Methods:Rats were randomly divided into the normal control group,the CUMS model group,the Venlafaxine group,and the Radix Paeoniae Alba groups ofhigh-dose and low-dose.The behavioral indicators of depression were used to evaluate the efficacy of Radix Paeoniae Alba.^(1)H-NMRmetabolomicstechnology combined with multivariate statistical analysis was applied to screen the differential metabolites related to depression,and the changes of endogenous metabolites were analyzed after the interventions of Radix Paeoniae Albaof high-dose and low-dose.Results:Compared tothose in the normal control group,the behavioral indicators of the rats changed significantly in the CUMS model group,that is,the body weight,the numbers of crossings and upright standing in the open field,as well as the sucrose preference rate decreased significantly(P<0.001),and the immobility time of forced swimming increased significantly(P<0.001).1H-NMRmetabonomicsresults showed 24 differential metabolites and 10 metabolic pathways were affected in the CUMS model group.Radix Paeoniae Alba could significantly adjust all metabolites and exerted antidepressant effects by affecting all metabolic pathways,which included D-glutamine and D-glutamate metabolism,Glutathione metabolism and Glycine metabolism.Conclusion:Radix Paeoniae Alba can improve the depression-like behavior of the CUMSrats and regulate the metabolic disorders of endogenous metabolites in liver.The mechanism may be related to the metabolic pathways of D-glutamine,D-glutamate,Glutathione and Glycine.