引火汤改善OVX+CUMS小鼠抑郁行为的代谢组学研究  

Metabonomics study on Yinhuo Tang improving depressive behavior in OVX+CUMS mice

作　　者：徐红丹 胡晶[1] 丁亚明[1] 张悦[3] 张宁 XU Hong-dan;HU Jing;DING Ya-ming;ZHANG Yue;ZHANG Ning(Department of Pharmacy,Wuxi Health Higher Vocational and Technical School,Wuxi 214000,China;Post Doctoral Station of Traditional Chinese Medicine of Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]无锡卫生高等职业技术学校药学系,无锡214000 [2]黑龙江中医药大学中药学博士后流动站,哈尔滨150040 [3]黑江中医药大学药学院,哈尔滨150040

出　　处：《药物分析杂志》2023年第12期2030-2037,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金(青年科学基金项目)(82003975);黑龙江省卫生健康委科研课题(2020-301);无锡市卫生健康委科研项目面上项目(M202170);黑龙江中医药大学基金项目(2018pt04,2017SEC02)。

摘　　要：目的:运用血清代谢组学的方法探索引火汤(Yinhuo Tang)对卵巢摘除(OVX)联合慢性不可预见性轻度应激(CUMS)小鼠抑郁样行为改善作用的机制。方法:45只昆明小鼠随机分为假手术组(sham组)、去卵巢模型组(OVX+CUMS组)和引火汤组,采用OVX+CUMS复制绝经后抑郁症(PMD)模型。旷场试验和强迫游泳试验观察小鼠的抑郁样行为;HE染色观察各组小鼠海马神经元状态;利用代谢组学方法观察各组小鼠体内血清差异代谢产物的变化,并分析其内在的生物学意义。结果:行为学结果显示,引火汤给药后OVX+CUMS小鼠的抑郁样行为明显改善;HE染色结果显示,引火汤给药后海马神经元形态呈正常现象。代谢组学研究结果显示,引火汤给药后小鼠血液的代谢轮廓均有显著的回调趋势,共鉴定差异代谢产物11个,包括柠檬酸、蒎酸、鞘磷脂、鞘氨醇1-磷酸、前列腺素J2、α-二吗啉酸、(S)-3-羟基丁酸、磷脂酰肌醇、对甲酚葡糖苷酸、对甲酚硫酸盐和酪氨酸有明显回调作用。结论:引火汤能够改善OVX+CUMS诱导抑郁小鼠的抑郁样行为,其作用机制可能是通过调节亚油酸代谢、柠檬酸循环、鞘脂代谢、谷氨酸代谢、乙醛酸和类固醇激素生物合成代谢通路实现的。Objective:To study the mechanism of Yinhuo Tang in improving depression like behavior in ovariectomized(OVX)combined with chronic unpredictable mild stress(CUMS)mice was explored by using the method of serum metabolomics.Methods:Forty-five Kunming mice were randomly divided into sham operation group,ovariectomy model group and Yinhuo Tang group.OVX+CUMS were used to replicate the postmenopausal depression(PMD)model.Open field test and forced swimming test were used to observe the depression like behavior of mice.HE staining was used to observe the state of hippocampal neurons in each group.Metabonomics method was used to observe the changes of serum differential metabolites in each group of mice,and its internal biological significance was analyzed.Results:The behavioral results showed that the depression like behavior of OVX+CUMS mice was significantly improved after administration of Yinhuo Tang.HE staining showed that the morphology of hippocampal neurons was normal.The results of metabonomics study showed that the metabolic profile of blood in mice after administration of Yinhuo Tang had a significant callback trend,and a total of 11 differential metabolites were identified,including citric acid,pinellic acid,sphingomyelin,sphingosine 1-phosphate,prostaglandin J2,alpha-dimorphecolic acid,(S)3-hydroxybutyric acid,PI[16∶0/22∶4(10Z,13Z,16Z,19Z)],p-cresol glucuronide,p-cresol sulfate and tyrosine,which had obvious callback effects.Conclusion:Yinhuo Tang can improve the depression like behavior of OVX+CUMS induced depression mice,and its mechanism may be achieved by regulating linoleic acid metabolism,citric acid cycle,sphingolipid metabolism,glutamate metabolism,glyoxylic acid and steroid hormone biosynthesis metabolic pathway.

关 键 词：绝经后抑郁症 代谢组学 引火汤 卵巢切除 慢性不可预知性刺激 

分 类 号：R917[医药卫生—药物分析学]