摘要
目的:探究百合地黄汤对抑郁症大鼠血清及粪便代谢组学的影响,筛选差异代谢物和代谢通路。方法:60只大鼠适应性饲养7 d后,随机分为正常组(10只)和应激组(50只),采用孤养和慢性不可预知性温和应激刺激制备大鼠抑郁症模型,造模成功的大鼠随机分为模型组,阳性对照组,百合地黄汤高、中、低剂量组,每组10只。给予百合地黄汤后,采用糖水偏好试验和旷场试验进行药效学评价;收集大鼠粪便和血清,应用LC-MS方法对大鼠血清和粪便进行非靶向代谢组学分析后,采用偏最小二乘方判别分析(OPLS-DA)和主成分分析(PCA),并联合t-test和变量投影重要性(VIP)筛选差异代谢物,应用KEGG数据库以及Metaboanalyst 5.0软件对差异代谢物进行通路富集。结果:与正常组大鼠比较,模型组大鼠体质量、糖水偏爱度和自主活动明显减少,给予百合地黄汤后,大鼠的抑郁样行为明显减少,抑郁大鼠的糖水偏爱度和在旷场中的自主活动明显增加。在代谢组学分析中,血清中共筛选出苯丙氨酰苯丙氨酸、5,6-二氢尿苷、L-谷氨酰胺等13个差异代谢物和丙氨酸、天冬氨酸和谷氨酸代谢以及类固醇激素生物合成等10条代谢通路,粪便中共筛选出L-甲硫氨酸、5-羟赖氨酸、α-生育三烯酚和次胆酸等10个差异代谢物以及甘油磷脂代谢、半胱氨酸和甲硫氨酸代谢等5条代谢通路。结论:百合地黄汤可能通过调节抑郁症大鼠的氨基酸、类固醇激素和甘油磷脂等代谢改善大鼠的抑郁样行为。
Objective:To explore the effects of Baihe Dihuang Decoction on serum and fecal metabolomics of depressed rats,and screen differential metabolites and metabolic pathways.Methods:After adaptive feeding for 7 days,60 rats were randomly divided into a normal group(10 rats)and a stress group(50 rats).The rat model of depression was prepared by solitary feeding and chronic unpredictable mild stress stimulation.After administration of Baihe Dihuang Decoction,the pharmacodynamics were evaluated by sugar water preference test and open field test.Meanwhile,faeces and serum were collected and their non-targeted metabolomics analyses were conducted using LC-MS method.After that,orthogonal partial least squares-discriminant analysis(OPLS-DA)and principal component analysis(PCA),combined with t-test and variable importance in projection(VIP),were employed to screen differential metabolites.KEGG database and metaboanalyst 5.0 software were used for pathway enrichment of screened differential metabolites.Results:Compared with the normal rats,the weight,sugar preference and autonomous activities of the model group rats were significantly reduced,while the depression like behavior of the rats was significantly reduced after Baihe Dihuang decoction was administered to the animals,and the sugar preference and autonomous activities in the open field of the depression rats were significantly improved.During metabolomics analysis,13 differential metabolites such as phenylalanyl phenylalanine,5,6-dihydrouridine and L-glutamine,and 10 metabolic pathways including alanine,aspartate and glutamate metabolism and steroid hormone biosynthesis were screened out in serum.A total of 10 differential metabolites,including L-methionine,5-hydroxyllysine,alpha-tocotrienol and hypocholic acid,and 5 metabolic pathways,including glycerophospholipid metabolism and cysteine and methionine metabolism,were screened out in feces.Conclusion:Baihe Dihuang Decoction may improve the depression like behavior of rats by regulating the metabolism of amino acids,steroid hormones and glycerol phospholipids in rats with depression.
作者
冯雪
刘雅清
刘滨
王敦方
刘丽
朱琳
刘海帆
张彩娟
杨伟鹏
FENG Xue;LIU Yaqing;LIU Bin;WANG Dunfang;LIU Li;ZHU Lin;LIU Haifan;ZHANG Caijuan;YANG Weipeng(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Heilongjiang University of Chinese Medicine,Harbin 150040,China)
出处
《中医药学报》
CAS
2023年第9期36-45,共10页
Acta Chinese Medicine and Pharmacology
基金
中国中医科学院中药研究所自主申报项目(ZXKT20033)。
关键词
百合地黄汤
抑郁症
代谢组学
差异代谢物
代谢通路
Baihe Dihuang Decoction
Depression
Metabonomics
Differential metabolites
Metabolic pathways
