Non-Targeted Metabolomic Profiling of Coronary Heart Disease Patients With Taohong Siwu Decoction Treatment
Non-Targeted Metabolomic Profiling of Coronary Heart Disease Patients With Taohong Siwu Decoction Treatment
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桃红四物汤治疗冠心病患者的非靶向代谢组学分析
DOI：
10.3389/fphar.2020.00651
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发表时间：
2020-05-08
影响因子：
5.6
通讯作者：
Liu, Xiuhua
中科院分区：
文献类型：
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作者：
Tao, Tianqi;He, Tao;Liu, Xiuhua
中医药是改善冠心病(CHD)预后的补充和替代疗法之一。桃红四物汤(THSWD)是一种具有活血作用的传统中药，临床上对冠心病有一定的疗效。然而，THSWD的潜在机制仍不清楚。为了全面了解血脉的物质基础，从中医理论上研究活血中药治疗冠心病所涉及的差异代谢物具有重要意义。因此，本研究调查了CHD患者的血清代谢谱，以确定THSWD组和安慰剂组之间的差异代谢物。入选冠心病患者11例，随机双盲法分为两组。血清样本采用基于串联质谱仪的非靶向超高效液相色谱代谢组学检测方法。皮尔逊相关分析用于评估已鉴定的代谢物与冠心病临床血清指标之间的相关性。结果表明，冠心病患者血清中共有513种代谢产物，其中27种代谢途径在两组间存在显著差异，涉及29条代谢途径。在差异代谢物中，与安慰剂组相比，THSWD上调了脂肪酸代谢中的琥珀酸肉碱和半胱氨酸和蛋氨酸代谢中的5‘-甲硫腺苷。然而，与安慰剂组相比，THSWD下调了参与FA代谢的藜芦酸、参与FA代谢的琥珀酸、参与三羧酸循环的琥珀酸、参与戊糖磷酸途径的葡萄糖酸、葡萄糖内酯和d-葡萄糖、参与甘油磷脂代谢的甘油磷胆碱、参与氨基酸代谢的8，9-二羟基二十碳三烯酸(8，9-DiHETrE)、L-赖氨酸、N-乙酰-L-天冬氨酸、N-α-乙酰-L-天冬氨酸、马尿酸、吲哚硫酸盐和3-氨基丙酸。此外，琥珀酸肉碱、戊二酸、琥珀酸、d-葡萄糖、葡萄糖酸、L-赖氨酸、N-α-乙酰-L-天冬酰胺、5‘-甲硫腺苷、硫代吲哚、8，9-二HETrE和3-氨基丙酸与总胆固醇或低密度脂蛋白有关。琥珀酰肉碱、藜芦酸、葡萄糖内酯、N-乙酰基-L-天冬氨酸、N-α-乙酰基-L-天冬酰胺、马尿酸和5‘-甲硫腺苷与活化部分凝血活酶时间相关。提示甘油磷胆碱、8，9-二HETrE、5‘-甲基硫代腺苷、马尿酸、硫代吲哚和3-氨基丙酸可能是THSWD治疗冠心病患者“血”的部分物质基础。
Traditional Chinese medicine is one of the complementary and alternative therapies to improve the prognosis of coronary heart disease (CHD). Taohong Siwu Decoction (THSWD), a classical traditional Chinese medication that promotes blood circulation, is clinically beneficial in CHD. However, the underlying mechanism of THSWD is still unclear. To comprehensively understand the material foundation of the "blood", it is significantly important to study the differential metabolites involved in the treatment of CHD with Chinese medicinal herb promoting blood circulation in TCM theory. Hence, this study investigated the metabolic profiles of the serum in CHD patients to determine the differential metabolites between the THSWD group and the placebo group. Eleven CHD patients were recruited and divided into two groups randomly and double-blindly. Serum samples were determined by performing non-targeted ultra-performance liquid chromatography with tandem mass spectrometry-based metabolomics. Pearson's correlation analysis was used to assess the association between identified metabolites and clinical serum indexes of CHD. Based on the result, a total of 513 metabolites were found in the serum of CHD patients, of which 27, involved in 29 metabolic pathways, were significantly different between the two groups. Among the differential metabolites, THSWD upregulated succinylcarnitine in fatty acid metabolism and 5 '-methylthioadenosine in cysteine and methionine metabolism compared with the placebo group. However, THSWD downregulated pelargonic acid, involved in FA metabolism; succinate, involved in the tricarboxylic acid cycle; gluconic acid, gluconolactone, and d-glucose, involved in pentose phosphate pathway; glycerophosphocholine, involved in glycerophospholipid metabolism; 8,9-dihydroxyeicosatrienoic acid (8,9-DiHETrE), l-lysine, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, indoxyl sulfate, and 3-ureidopropionate involved in amino acid metabolism compared with the placebo group. Moreover, succinylcarnitine, pelargonic acid, succinate, d-glucose, gluconic acid, l-lysine, N-alpha-acetyl-l-asparagine, 5 '-methylthioadenosine, indoxyl sulfate, 8,9-DiHETrE, and 3-ureidopropionate were associated with total cholesterol or low-density lipoprotein. Succinylcarnitine, pelargonic acid, gluconolactone, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, and 5 '-methylthioadenosine were associated with activated partial thromboplastin time. Our findings indicated that glycerophosphocholine, 8,9-DiHETrE, 5 '-methylthioadenosine, hippurate, indoxyl sulfate, and 3-ureidopropionate might constitute the partial material foundation of the "blood" in CHD patients treated with THSWD.