太空养心丸干预模拟失重大鼠的血清代谢组学分析  

Serum Metabolomics of Simulated Weightless Rats Treated with Taikong Yangxin Pills

作　　者：刘晓弟 范雪梅 王义明 闫梦佳[1] 李勇枝 王佳平[4] 刘军莲[4] 罗国安[1,3] LIU Xiaodi;FAN Xuemei;WANG Yiming;YAN Mengjia;LI Yongzhi;WANG Jiaping;LIU Junlian;LUO Guoan(School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China;School of Pharmaceutical Sciences,Tsinghua University,Beijing 100084,China;Department of Chemistry,Tsinghua University,Beijing 100084,China;China astronaut Research and Training Center,Beijing 100094,China)

机构地区：[1]广东药科大学中药学院,广州510006 [2]清华大学药学院,北京100084 [3]清华大学化学系,北京100084 [4]中国航天员科研训练中心,北京100094

出　　处：《中国实验方剂学杂志》2025年第2期147-153,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：1226工程卫生专业重大项目(AWS16J018)。

摘　　要：目的:基于代谢组学研究太空养心丸对模拟失重大鼠代谢水平的影响,探讨其代谢作用机制。方法:在地面模拟太空舱环境内,采用尾部悬吊法建立模拟失重大鼠模型。将大鼠随机分为舱外正常组、舱内正常组、模型组和高(3.0 g·kg^(-1))、低剂量(1.5 g·kg^(-1))太空养心丸给药组,灌胃给药28 d。采用超高效液相色谱-四级杆-飞行时间质谱法(UPLC-Q-TOF/MS)检测大鼠血清内源性代谢物水平,通过主成分分析(PCA)和正交偏最小二乘法-判别分析(OPLS-DA)处理数据以筛选差异代谢物、潜在生物标志物,然后利用MetaboAnalyst 5.0进行通路富集分析,阐释药物的代谢调控机制。结果:相比舱外正常组,舱内正常组大鼠体内14-羟基十六烷酸、亚油酸、α-亚麻酸等13个代谢物含量显著升高(P<0.05),提示太空舱环境主要影响了大鼠体内α-亚麻酸和亚油酸代谢。相比舱内正常组,模拟失重模型组大鼠体内4-咪唑酮-5-丙酸、异柠檬酸/柠檬酸及L-酪氨酸等14个代谢物的血清水平明显降低(P<0.05);太空养心丸干预后,这14个代谢物的代谢水平全部显著回调(P<0.05)。通路富集分析发现尾部悬吊法失重及药物干预主要涉及苯丙氨酸、酪氨酸和色氨酸的生物合成,酪氨酸代谢、组氨酸代谢及柠檬酸循环等代谢途径。结论:模拟太空舱环境和尾部悬吊模拟失重均会对大鼠体内代谢水平造成影响,太空养心丸能够通过调节多种氨基酸及能量代谢相关通路改善失重模型大鼠的代谢异常。Objective:To study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism.Methods:In the simulated space capsule environment on the ground,the rat model of simulated weightlessness was established by the tail suspension method.Rats were randomly grouped as follows:out-of-capsule control,in-capsule control,model,and high(3.0 g·kg^(-1))and low(1.5 g·kg^(-1))doses of Taikong Yangxin Pills,and they were administrated with corresponding drugs by gavage for 28 days.The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS).The obtained data were processed by principal component analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA)to screen for differential metabolites and potential biomarkers.MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug.Results:Compared with the out-of-capsule control group,the in-capsule control group showed elevated levels of thirteen metabolites,including 14-hydroxyhexadecanoic acid,linoleic acid,andα-linolenic acid(P<0.05),which suggested that the space capsule environment mainly affected the metabolism ofα-linolenic acid and linoleic acid in the rats.Compared with the in-capsule control group,the model group showed lowered levels of fourteen metabolites,including 4-imidazolone-5-propionic acid,isocitric acid/citric acid,and L-tyrosine(P<0.05),which were recovered after the treatment with Taikong Yangxin pills(P<0.05).The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine,tyrosine,and tryptophan biosynthesis,tyrosine metabolism,histidine metabolism,and citric acid cycle.Conclusion:The simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of ra

关 键 词：太空养心丸 模拟失重模型 代谢组学 超高效液相色谱-四级杆-飞行时间质谱法(UPLC-Q-TOF/MS) 作用机制 

分 类 号：R285[医药卫生—中药学] R289[医药卫生—中医学] R287