基于代谢组学方法研究阿司匹林丁香酚酯对大鼠代谢的影响  

Metabolomics-based approach to study effects of AEE on rat metabolism

作　　者：陶琦 范丽萍 过海天 马宁 刘希望[1] 杨亚军[1] 李剑勇[1] TAO Qi;FAN Liping;GUO Haitian;MA Ning;LIU Xinwang;YANG Yajun;LI Jianyong(Key Laboratory of New Animal Drug Project of Gansu Province/Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs,Lanzhou Institute of Husbandry and Pharmaceutical Sciences,Chinese Academy of Agricultural Sciences,Lanzhou 730050,China;College of Animal Medicine,Hebei Agricultural University,Baoding Hebei 071000,China)

机构地区：[1]中国农业科学院兰州畜牧与兽药研究所农业农村部兽用药物创制重点实验室/甘肃省新兽药工程重点实验室,甘肃兰州730050 [2]河北农业大学动物医学院,河北保定071000

出　　处：《中国兽医学报》2024年第8期1782-1792,共11页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(32273069,32373071)。

摘　　要：探究阿司匹林丁香酚酯(aspirin eugenol ester,AEE)对大鼠代谢的影响,首先配制合适浓度的AEE混悬液。将Wistar大鼠随机分为3组,分别为正常组、AEE低剂量组(18 mg/kg)和AEE高剂量组(72 mg/kg)。给药组大鼠每日灌服给药1次,正常组Wistar大鼠每日灌服1次等体积的0.5%羧甲基纤维素钠溶液。连续灌服7 d后收集粪便和尿液,应用超高效液相色谱-四级杆飞行时间串联质谱法(UPLC-QTOF-MS/MS)对大鼠粪便和尿液进行非靶向代谢组学分析,并进行Metabo Analyst 5.0代谢通路富集分析。结果显示,本试验所选的AEE剂量对大鼠的生长未见影响;在大鼠粪便与尿液中分别鉴定出10个和8个差异代谢物,涉及到的代谢通路主要有苯丙氨酸、酪氨酸和色氨酸的生物合成,苯丙氨酸代谢、类固醇激素生物合成、不饱和脂肪酸的生物合成、氨基糖和核苷酸糖代谢、脂肪酸生物合成和β-丙氨酸代谢等。结果表明,给药组大鼠体质量无显著影响(P>0.05),但大鼠的代谢受到影响。粪便代谢物主要涉及的代谢通路包括:不饱和脂肪酸的生物合成、酪氨酸代谢、脂肪酸生物合成和类固醇激素生物合成;尿液代谢物主要涉及的代谢通路包括:嘌呤代谢、脂肪酸生物合成、精氨酸和脯氨酸代谢。因此,AEE对大鼠代谢影响主要与调节脂质代谢、氨基酸代谢、能量代谢等密切相关。试验结果为AEE在动物体内药效和临床应用提供一定的理论参考。The effect of aspirin eugenol ester(AEE)on the metabolism of rats was investigated to provide theoretical references for the clinical rational use of the drug.Firstly,the appropriate concentration of AEE suspension was prepared.Wistar rats were randomly divided into three groups:the normal group,the AEE low-dose group(18 mg/kg),and the AEE high-dose group(72 mg/kg).The rats in the dosing group were dosed once daily,and the Wistar rats in the normal group were dosed once daily with an equal volume of 0.5%sodium carboxymethylcellulose solution.The feces and urine were collected after 7 days of continuous gavage,and the feces and urine were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-QTOF-MS/MS)for non-targeted metabolomics and Metabo Analyst 5.0 was used for metabolic pathway enrichment.The results showed that the dose of AEE selected in this experiment was not toxic to the growth of rats.The results of the metabolomics study found that10and 8differential metabolites were identified in rat feces and urine,respectively,involving metabolic pathways such as phenylalanine,tyrosine and tryptophan biosynthesis,phenylalanine metabolism,steroid hormone biosynthesis,biosynthesis of unsaturated fatty acids,aminosugar and nucleotide sugar metabolism,fatty acid biosynthesis,andβ-alanine metabolism.AEE had no significant effect on the body weight of rats(P>0.05),but AEE could affect the metabolism of rat organism.Fecal metabolites were mainly involved in metabolic pathways including unsaturated fatty acid biosynthesis,tyrosine metabolism,fatty acid biosynthesis,and steroid hormone biosynthesis;urinary metabolites were mainly involved in metabolic pathways including purine metabolism,fatty acid biosynthesis,arginine,and proline metabolism.Therefore,the metabolic effects of AEE on rats are mainly closely related to the regulation of lipid metabolism,amino acid metabolism,and energy metabolism.The results of this experiment can provide some references for the efficac

关 键 词：阿司匹林丁香酚酯(AEE) 粪便 尿液 代谢组学 UPLC-QTOF-MS/MS 

分 类 号：S859.7[农业科学—临床兽医学]