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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2020, Vol. 25 ›› Issue (3): 246-256.doi: 10.12092/j.issn.1009-2501.2020.03.002

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Study on high on-aspirin platelet reactivity in diabetic mice based on metabonomics

ZHANG Haowen 1, ZHU Yejin 2, WU Xiang 3, CHEN Hanyu 4, SONG Yulei 1, BIAN Yaoyao 1, HAO Haiping 2, CHEN Xiaohu 3   

  1. 1 Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China; 2 Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, China; 3 Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu, China; 4 School of Rehabilitation Science, Nanjing Normal University of Special Education, Nanjing 210038, Jiangsu, China
  • Received:2019-06-05 Revised:2020-02-22 Online:2020-03-26 Published:2020-04-13

Abstract: AIM: To explore the underlying mechanism of aspirin-related high on-aspirin platelet reactivity (HAPR) in diabetic state from the perspective of endogenous metabolic changes in metabolomics. METHODS:Type 2 diabetes mellitus (T2DM) mice model was established by the combination treatment of high-fat diet and streptozotocin injections. Mice were randomly divided into Normal group, T2DM group, Normal+aspirin group and T2DM+aspirin group. GC/TOF-MS was used to determine the plasmatic endogenous metabolites of mice. The data were analyzed applying multivariate statistical method. RESULTS:The expression of platelet CD62P and ratio of TXB2/6-keto-PGF1α in the plasma of female T2DM mice showed no significant difference compared with that of the model group. The degree of divergence between normal and normal+aspirin groups was significantly greater than that between T2DM and T2DM+aspirin groups. Biochemical metabolic pathway analysis revealed that HAPR in diabetic mice was linked to glycolysis, gluconeogenesis, pyruvate metabolism, citric acid cycle, ascorbic acid metabolism, and arachidonic acid metabolic pathways. CONCLUSION:The different metabolites obtained in metabolome assay suggests that the HAPR in diabetic state involved several different metabolic pathways, which can better elucidate the biological mechanism of diabetes-associated HAPR.

Key words: metabonomics, diabetes, high on-aspirin platelet reactivity

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