卡托普利干预自发性高血压大鼠血清代谢组学研究

摘要

目的通过代谢组学方法研究卡托普利干预自发性高血压大鼠血清内源性代谢物的变化，进一步探索卡托普利的作用机制。方法采用快速高分离液相－四级杆飞行时间串联质谱联用技术采集大鼠血清内源性代谢物信息，经偏最小二乘法判别分析，识别显著差异的变量，鉴定潜在生物标志物。结果正常组、模型组、卡托普利组的血清内源性代谢物、代谢模式发生了明显变化。经数据库查询共确定了4个生物标记物及其代谢途径，与血管内皮功能密切相关。结论代谢组学从机体整体代谢角度揭示了卡托普利保护血管内皮功能的可能作用机制，在阐释药物复杂的作用机制方面显示出了独特的潜力。%Aims To analyze the intervention effect of Captopril on serum endogenous metabolites alternations in spontaneous hypertension rats ( SHR) and to investi-gate possible therapeutic mechanism .Methods The rapid resolution liquid chromatography/quadrupole-time of flight tandem mass spectrometry ( RRLC-Q-TOF-MS) and technology coupled with partial least squares discriminant analysis ( PLS-DA ) processed by SIMCA-P software were used to distinguish significantly different variables and identify potential biomarkers . Results Compared to the normal group , metabolic profiling changed significantly in model group and Cap-toril group .Totally 4 metabolins and their metabolic pathways were detected , which were closely related to the endothelial function .Conclusion Metabolomics reveals possible therapeutic mechanism of Captopril for protecting endothelial function from overall metabolism of the body .It also shows unique potential in terms of interpretation of the complex mechanisms of drugs .