基于核磁共振的益母草碱抗急性心肌缺血的代谢组学研究  

~1H NMR-based metabolomics study of intervention effects of leonurine on acute myocardial ischemia in rats

作　　者：刘成鹏[1] 殷晓芹[2] 李玉琴[1] 罗珊珊[3] 朱清[1,3] 李俊旭[1] 朱依谆[3] 

机构地区：[1]南通大学药学院,江苏南通226001 [2]南通大学附属医院药剂科,江苏南通226001 [3]复旦大学药学院,上海201210

出　　处：《中国药理学通报》2017年第9期1235-1242,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81373390);国家重点基础研究发展计划资助项目(No 2010CB912600);江苏省自然科学基金资助项目(No BK20130396)

摘　　要：目的应用核磁共振(NMR)代谢组学技术研究急性心肌缺血以及益母草碱给药大鼠血浆中代谢物组的变化,探讨益母草碱抗心肌缺血作用的机制。方法应用1H NMR分析假手术组、模型组、益母草碱给药组大鼠血浆代谢物组,应用模式识别多变量统计方法研究模型组与假手术组及给药组之间的代谢物组差异。结果正交偏最小二乘法-判别分析(OPLS-DA)结果显示,模型组与假手术组相比有6个代谢物(丙氨酸、赖氨酸、甘氨酸、肌酸、N-乙酰化及O-乙酰化糖蛋白)水平明显增加,而益母草碱干预治疗能明显降低模型组丙氨酸、赖氨酸、甘氨酸水平,并增加胆碱、磷酸胆碱、鲨肌醇含量。结论益母草碱能通过纠正急性心肌缺血氨基酸代谢紊乱,上调胆碱以及肌醇代谢通路发挥心肌保护作用。该研究为评价益母草碱抗心肌缺血作用提供了有力分析手段,并为研究其作用机制提供新的思路。Aim To investigate metabolomic profiles of acute myocardial ischemia（ AMI） in rat plasma and explore the intervention effects and its mechanism of leonurine using a metabolomics approach based on nuclear magnetic resonance（ NMR）. Methods The plasma metabolomic characteristics in rats of sham group,AMI model group,and leonurine-treated group were detected by -1H NMR,and the different metabolites between AMI group and sham group or leonurine-treated group were analyzed by pattern recognition and multivariate data analysis. Results Orthogonal partial least squares discriminant analysis（ OPLS-DA） demonstrated that six metabolites related to AMI were screened out,including alanine,lysine,glycine,creatine,N-acetyl glycoprotein,and O-acetyl glycoprotein and all their levels were elevated in AMI group compared to sham group. Treatment of leonurine decreased the levels of alanine,lysine,and glycine,and increased the levels of choline,phosphocholine,and scyllo-inositol compared with the model group. Conclusions Leonurine can improve amino acid metabolism disorder under AMI conditions and enhance the function of choline and inositol pathway,which may explain its cardioprotective effect. The developed metabolomics approach in this study is a powerful tool for the investigation of the cardioprotective effect of leonurine and provide a new insight to understand its pharmacological mechanism.

关 键 词：益母草碱 急性心肌缺血 核磁共振 代谢组学 模式识别 多变量统计 

分 类 号：R-332[医药卫生] R284.1