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基于代谢组学技术研究不同剂量肾上腺素血瘀证模型的作用机制 被引量:1

Mechanism of Blood Stasis Syndrome Model Induced by Different Doses of Epinephrine Based on Metabolomics Technology
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摘要 目的:运用代谢组学的方法,探讨不同剂量肾上腺素构建大鼠慢性血瘀证模型的作用机制及其关键代谢物。方法:连续皮下注射不同剂量肾上腺素构建慢性血瘀模型,测定大鼠血液流变学、凝血四项等指标进行模型判断,通过反相液相色谱-串联质谱法(RPLC-MS)与亲水作用液相色谱法-质谱联用(HILIC-MS)技术进行检测,采用偏最小二乘判别分析(PLS-DA)研究给药前后模型内源性代谢物变化。结果:与正常对照组比较,高中低剂量肾上腺素组大鼠全血黏度在不同切变率下均显著升高,凝血四项检测中凝血酶原时间和纤维蛋白原含量显著升高,体质量显著性下降,代谢组实验结果显示正常组与高中剂量肾上腺素组之间区分明显,其分离趋势与给药剂量密切相关,在RPLC-MS模式下发现了葡萄糖、乙酰辅酶A、二十碳五烯酸等代谢物,同时在HILIC-MS模式下发现了牛磺酸、油酸等代谢物,2种检测模式下共发现了与气滞血瘀模型发病机制及演化过程相关的28个潜在生物标志物。结论:一定剂量的肾上腺素会导致慢性血瘀证的发生,随着给药剂量的增加,其造模程度也随着变化。根据机体内与给药剂量呈一定相关性的代谢变化来看,慢性血瘀证的作用机制及其演化过程可能与葡萄糖代谢、脂肪酸代谢、胆酸代谢、肉碱代谢、酪氨酸及色氨酸代谢等代谢相关。 Objective:To explore the mechanisms and key metabolites of a chronic blood stasis syndrome model in rats induced by different doses of epinephrine through metabolomics.Methods:The chronic blood stasis syndrome model was established by continuous subcutaneous injection of different doses of epinephrine.Hemorheological parameters and coagulation indicators were measured to assess the model.Detection was performed using reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS)and hydrophilic interaction liquid chromatography-mass spectrometry(HILIC-MS).Partial least squares discriminant analysis(PLS-DA)was used to analyze the changes in endogenous metabolites before and after administration.Results:Compared with the normal control group,the high-,medium-,and low-dose epinephrine groups showed significant increases in whole blood viscosity at different shear rates,elevated prothrombin time and fibrinogen levels in the coagulation profile,and decreased body weight.Metabolomics analysis revealed clear differentiation between the normal control group and the high-dose epinephrine group.The separation trend was closely related to the dosage.Metabolites such as glucose,acetyl-CoA,and eicosapentaenoic acid were identified in the RPLC-MS mode,while metabolites such as taurine and oleic acid were detected in the HILIC-MS mode.Twenty-eight potential biomarkers associated with the pathogenesis and progression of qi stagnation and blood stasis syndrome were identified in both modes.Conclusion:A certain dose of epinephrine can induce chronic blood stasis syndrome,and the modeling degree varies with the dosage.Metabolic changes related to glucose metabolism,fatty acid metabolism,bile acid metabolism,carnitine metabolism,and tryptophan and tyrosine metabolism may be involved in the mechanism and progression of chronic blood stasis syndrome based on the correlation with the dosage-related changes in the body.
作者 胡广 杨会珍 张国瑗 李瑛 任常英 孙明谦 林力 HU Guang;YANG Huizhen;ZHANG Guoyuan;LI Ying;REN Changying;SUN Mingqian;LIN Li(Institute of Basic Medical Sciences,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)
出处 《世界中医药》 CAS 2023年第12期1672-1678,1683,共8页 World Chinese Medicine
基金 国家自然科学基金项目(81872992)——血府逐瘀汤活血功效和理气功效的物质基础研究 中国中医科学院科技创新工程项目(C12021A04508,C12021A01707)——基于体内过程的血府逐瘀汤组方功效配伍研究,基于代谢组学技术研究龙柴降血颗粒治疗骨髓增殖性肿瘤的作用机制。
关键词 液质联用 代谢组学 肾上腺素 慢性血瘀证 生物标志物 血小板聚集 能量代谢 色氨酸代谢 LC-MS Metabolomics Epinephrine Chronic blood stasis syndrome Biomarkers Platelet aggregation Energy metabolism Tryptophan metabolism
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