基于代谢组学探讨丹蒌片治疗冠心病稳定型心绞痛痰瘀互结证疗效机制

Efficacy mechanism of Danlou Tablets in the treatment of phlegm and blood stasis syndrome in stable angina pectoris of coronary heart disease based on metabolomics

目的:研究丹蒌片治疗冠心病稳定型心绞痛痰瘀互结证的临床疗效和机制。方法:多中心纳入冠心病稳定型心绞痛痰瘀互结证患者64例,随机分为西药组和中药组,每组32例。西药组使用西药标准化治疗,中药组在此基础上加服丹蒌片。比较心绞痛发作次数,应用超高液相色谱质谱技术筛选血清差异代谢物,分析代谢通路。结果:治疗后中药组心绞痛发作频次显著低于西药组,中药组和西药组治疗前后组内比较,各发现12、13个变化显著的差异代谢物;两组治疗后组间比较,发现12个变化显著的差异代谢物,对差异代谢物进行富集分析后发现丹蒌片可影响花生四烯酸代谢通路和咖啡因代谢通络。结论:丹蒌片可能含有类咖啡因物质,其代谢后产生1-甲基黄嘌呤发挥心血管保护作用,还可影响花生四烯酸所有代谢途径发挥心血管保护作用。

Objective:To observe the efficacy and mechanism of Danlou Tablets in treating stable angina pectoris of coronary heart disease with phlegm and stasis syndrome by metabonomics.Methods:A total of 64 patients from multi-centre with stable angina pectoris of coronary heart disease with phlegm and blood stasis syndrome were enrolled.They were divided into traditional Chinese medicine group(32 cases) and western medicine group(32 cases) by central randomization system.The western medicine group was treated with standardized treatment of stable angina pectoris,and the traditional Chinese medicine group was treated with standardized treatment of stable angina pectoris plus Danlou Tablets.The onset number of angina pectoris was compared.Serum samples were collected before and after treatment,which was analyzed by ultra high liquid chromatographymass spectrometry to screen serum differential metabolites and metabolic pathways.Results:After treatment,the onset number of angina pectoris in traditional Chinese medicine group was significantly lower than that in the western medicine group.By comparing the serum samples before and after treatment in the traditional Chinese medicine group and the western medicine group,12 and 13 different metabolites with significant changes were found respectively.By comparing the serum samples of western medicine group and traditional Chinese medicine group after treatment,12 significantly different metabolites were found.Through the enrichment analysis of different metabolites,it was found that Danlou Tablets had a significant effect on arachidonic acid metabolic pathway and caffeine metabolic pathway.Conclusion:Danlou Tablets may contain caffeine like substances and produce 1-methylxanthine to play a cardiovascular protective role.In addition,it can also play a cardiovascular protective role by affecting all the arachidonic acid metabolism pathway.