基于非靶向尿液代谢组学技术的原发性痛经不同进展阶段的生物学基础研究  

Study on biological basis of primary dysmenorrhea based in different progressive stages based on untargeted metabolomics

作　　者：于永洲 李娜[1,2] 崔晓燕 李哲 赵蓝青青[4] 刘琦 熊辉 YU Yong-zhou;LI Na;CUI Xiao-yan;LI Zhe;ZHAO Lan-Qing-qing;LIU Qi;XIONG Hui(Hebei Key Laboratory of Nerve Injury and Repair,Chengde Medical College,Chengde Hebei 067000,China;Institute of Basic Medical Research,Chengde Medical College,Chengde Hebei 067000,China;Hebei Institute for Drug and Medical Device Control,Shijiazhuang 050011,China;Hebei Key Laboratory of Study and Exploitation of Chinese Medicine,Chengde Medical College,Chengde Hebei 067000,China;the Research Institute of Medicine and Pharmacy,Qiqihar Medical University,Qiqihar Heilongjiang 161006,China)

机构地区：[1]承德医学院河北省神经损伤与修复重点实验室,河北承德067000 [2]承德医学院基础医学研究所,河北承德067000 [3]河北省药品医疗器械检定研究院,河北石家庄050011 [4]承德医学院河北省中药研究与开发重点实验室,河北承德067000 [5]齐齐哈尔医学院医药科学研究院,黑龙江齐齐哈尔161006

出　　处：《中国药理学通报》2023年第4期744-749,共6页Chinese Pharmacological Bulletin

基　　金：河北省高等学校科学技术研究项目(No QN2021008);河北省高校重点学科建设项目(冀教高[2013]4);河北省科技厅“技术创新引导专项-科技工作会商”项目。

摘　　要：目的 通过非靶向尿液代谢组学技术研究原发性痛经形成过程中大鼠的内源性代谢特征,探讨其潜在的生物学实质。方法 将20只SD大鼠随机分成空白组和模型组。模型组大鼠采用苯甲酸雌二醇联合缩宫素方法复制原发性痛经模型,空白组正常饮食饮水。采用超高效液相色谱-四极杆-飞行时间质谱联合多变量模式识别方法寻找差异性代谢物及核心代谢通路,使用MetaboAnalyst 5.0平台绘制受试者工作特征(receiver operating characteristic curve, ROC)曲线来评估核心代谢物临床诊断效能。结果 共筛选出马尿酸、苯乙醛、前列腺素G2、6-羟基-5-甲氧基吲哚葡萄糖醛酸等46种差异显著的小分子代谢物,涉及苯丙氨酸代谢,戊糖和葡萄糖醛酸酯的相互转化,花生四烯酸代谢3条核心代谢通路。ROC曲线进一步分析出4种核心生物标志物曲线下面积均大于0.7。结论 原发性痛经不同进展阶段呈现不同的代谢图谱,主要涉及脂肪酸代谢、糖类代谢和氨基酸代谢的紊乱,同时提取出的特征性生物标志物对于评估原发性痛经具有较高的诊断价值。Aim To explore its potential biological basis and the endogenous metabolic characteristics of urine during the formation of primary dysmenorrhea via untargeted urine metabolomics.Methods Twenty SD rats were randomly divided into control group and model group.The primary dysmenorrhea model was reproduced by estradiol benzoate combined with oxytocin,and the contrrol group took food and water freely.The differential metabolites and core metabolic pathways were found by multivariable pattern recognition method combined with ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry.The receiver operating characteristic(ROC)curve was drawn by metaboanalyst 5.0 platform to evaluate the clinical diagnostic efficacy of core metabolites.Results A total of 46 metabolites with significant differences,such as hippuric acid,phenylacetaldehyde,prostaglandin G2,6-hydroxy-5-methoxyindole glucuronide,were screened,mainly involving phenylalanine metabolism,pentose and glucuronate interconversions,and arachidonic acid metabolism.ROC curve showed that the area under the curve of four core biomarkers was greater than 0.7.Conclusions Different metabolic maps are presented in different progressive stages of primary dysmenorrhea,mainly involving the disorders of fatty acid metabolism,carbohydrate metabolism and amino acid metabolism.Meanwhile,the extracted characteristic biomarkers have high diagnostic value for the evaluation of primary dysmenorrhea.

关 键 词：原发性痛经 代谢组学 生物标志物 ROC曲线 生物学基础 尿液 

分 类 号：R-332[医药卫生] R349.1R446.12R711.51