基于代谢组学的抗心绞痛常见药物的比较

Metabolomic Based Comparison Study on Angina Pectoris Treated with Common Drugs

目的采用基于气相色谱-质谱(GC-MS)的代谢组学技术比较并评价单硝酸异山梨酯,曲美他嗪,复方丹参滴丸三种药物抗心绞痛作用机制。方法 40只SD大鼠分为模型组、正常对照组、单硝酸异山梨酯组、曲美他嗪组、复方丹参滴丸组5组,采用GC-MS技术对不同组别大鼠的血浆进行分析。并利用SIMCA-P软件对不同组之间代谢产物含量变化进行主成分分析(PCA)和偏最小二乘法判别分析(PLS-DA),初步揭示心绞痛生物标志物,为心绞痛药物筛选提供新的方法。结果代谢组学分析结果显示,模型组大鼠血浆中琥珀酸、延胡索酸、葡萄糖、柠檬酸、乳酸、尿素、甘氨酸、苯丙氨酸、异亮氨酸及肌苷等内源性代谢物有差异性变化(P<0.05),可视为心绞痛生物标志物。PCA和PLS-DA统计结果显示曲美他嗪组距离正常对照组最近,且所能回调的标志物较其他两组多,其抗心绞痛效果较优。结论三种药物都有明显的抗心绞痛效果,曲美他嗪效果较优;运用代谢组学技术分析了三种药物抗心绞痛有关标志物的调节作用并对其机制进行了初步比较研究,为药物药效的评价提供了新思路和新方法。

Objective To compare the different mechanism between isosorhide 5-mononitrate,Trimetazidine and Compound Danshan Dropping Pills in treatment for angina pectoris using C-C-MS by metabolornie approach. Methods Forty SD mrs were equally divided into the model group,the blank control group ,the isosorhide 5-mononitrategroup,the Trimetazidine group,and the Compound Danshen Dropping Pills group. Changes of metabolite contents were analyzed among different groups using GC-MS via principal component analysis （PCA） and partial least squares analysis （PLS-DA）using the SIMCA-P software Biornarkers of angina pectoris injury are initially revealed. The metabolornics study could offer a new method and tool for angina pectoris. Results Metaholomie analysis showed that the Trimetazidine group located closer to the blank control group,showing better efficacy than the other two groups. More perturbed metaholites were reversed by Tfimetazidine group. In the plasma of rats,succinic acid,2-butenedioic acid, d-glucose,citric acid, lactic acid,urea,glyeine,phenylalanine,1-isoleucine,creafinine,and so on had significant changes before and after myocardial ischemia. Conclusions Three drugs have significant efficacy,and Trimetazidine shows best effect. Metaholomic approach was applied in this study to analyze the regulation of hiomarkers and compare the mechanisms of the three drugs. These results provide new methods for the evaluation of drug efficacy.