基于1H—NMR技术研究心气虚证心力衰竭模型大鼠尿液代谢组学变化

目的观察心肌梗死后心力衰竭大鼠尿液代谢组学变化。方法将SD大鼠随机分为造模组与假手术组，采用左冠状动脉前降支结扎制造心肌梗死后心气虚证心力衰竭大鼠模型，于造模后第8周末收集尿液，利用核磁共振氢谱（1H—NMR）技术检测2组大鼠尿液小分子及大分子代谢物情况，建立大鼠尿液代谢图谱，并采用主成分分析（PCA）及正交偏最]bZ-乘判别分析（OPLS—DA）对代谢图谱进行主成分分析及模式判别，以观察心气虚证心力衰竭大鼠尿液代谢组学的变化。结果模型组与假手术组尿液小分子及大分子代谢物均能明显区分。与假手术相比，模型组3-羟基丁酸、乙酸、丙酮、磷脂酰胆碱、三甲胺、马尿酸含量升高；谷氨酰胺、肌肝、牛磺酸、柠檬酸、苹果酸、苯基丙氨酸含量下降。结论心肌梗死后心气虚证心力衰竭大鼠出现尿液代谢组学变化，差异代谢产物主要与能量代谢、糖代谢、脂代谢、氨基酸代谢紊乱及肾、胃肠道功能异常相关。

Research of urine metabonomics changes in heart failure rats with syndrome of heart-qi deficiency based on 1H-NMR method

Objective To observe the changes of urine metabonomics in heart failure rats after myocardial infarction.Methods The Sprague Dawley rats were randomly divided into a model group and a sham-operation group. Rat models of heart failure after myocardial infarction were established by ligating the left anterior descending coronary artery of the rats.At the end of 8th week of model establishment,the urine samples were collected and examined by H-nuclear magnetic resonance （1H-NMR）method. So the metabolic map of urine was built up, which was analyzed by principal component analysis （PCA）and partial least square discriminate analysis （PLS-DA）to observe the changes of urine metabonomics in heart failure rats.Results The macromolecule and micromolecule metabolites in urine in the model group and sham-operation group could be obviously distinguished. Compared with sham-operation group, the contents of 3-hydroxybutyric acid, acetic acid, acetone, phosphatidyl choline, trimethyl amine, hippuric acid were increased in the model gorup, while the contents of glutamine, creatinine, taurine, citric acid, malic acid, phenyl alanine were decreased.Conclusion There were changes of urine metabonomies in heart failure rats with syndrome of heart-qi deficiency after myocardial infarction, and the distinguished metabolites are mainly related to the disorders of energy metabolism, glucose metabolism, lipid metabolism, amino acid metabolism, as well as the dysfunctions of kidney, liver and gastrointestinal tract.