基于非靶向代谢组学探讨参附强心丸治疗慢性心力衰竭心肾阳虚证作用机制

Investigation on the mechanism of Shenfu Qiangxin Pills in the treatment of chronic heart failure in heart-kidney yang deficiency syndrome based on untargeted metabolomic

目的:采用代谢组学方法探索参附强心丸治疗慢性心力衰竭心肾阳虚证的机制,发掘与鉴定其潜在的生物标志物。方法:共纳入38例参附强心丸治疗的慢性心力衰竭患者,采用Agilent 1290 Infinity LC超高压液相色谱仪分别对其治疗前后血清样本进行代谢组学检测,正负离子模式合并后,鉴定等级在Level 2以上共1335种代谢物,采用偏最小二乘判别分析、正交偏最小二乘判别分析进行多元分析,并进行置换检验以检测模型可靠度。对筛选所得的差异代谢物进行KEGG通路富集分析。结果:参附强心丸治疗后,非靶向代谢组学共筛选出D-谷氨酰胺、L-高精氨酸等15种差异代谢物,涉及D-谷氨酰胺和D-谷氨酸代谢、精氨酸生物合成、嘧啶代谢、嘌呤代谢等18条代谢通路。KEGG富集结果显示谷氨酸能突触、GABA能突触、D-谷氨酰胺和D-谷氨酸代谢、近端小管碳酸氢盐回收、氮代谢、精氨酸生物合成6条通路为主要富集通路。结论:参附强心丸可能通过调控氨基酸代谢通路发挥对慢性心力衰竭的治疗作用。

Objective:To explore the mechanism of Shenfu Qiangxin Pills in the treatment of chronic heart failure in heart-kidney yang deficiency syndrome by using metabolomics method,explore and identify its potential biomarkers.Methods:Thirty-eight participants with chronic heart failure who received treatment with Shenfu Qiangxin Pills were included,and their serum samples of baseline and after treatment were used for metabolomics testing by UHPLC(1290 Infinity LC).A total of 1335 metabolites above Level 2 were identified,which were identified by the combination with positive ion modes and negative ion modes.Adopted partial least squares discrimination analysis,orthogonal projections to latent structures discriminant analysis for multivariate analysis,and tested the reliability of the model by using permutation test.The identified differential metabolites were subjected to KEGG pathway enrichment analysis.Results:After treatment with Shenfu Qiangxin Pills,a total of 15 differential metabolites such as D-glutamine and L-homoarginine,a total of 16 KEGG pathways such as D-Glutamine and D-glutamate metabolism,Arginine biosynthesis,Pyrimidine metabolism,Purine metabolism and so on.KEGG enrichment analysis showed 6 target pathway such as Glutamatergic synapse,GABAergic synapse,D-Glutamine and D-glutamate metabolism,Proximal tubule bicarbonate reclamation,Nitrogen metabolism,Arginine biosynthesis.Conclusion:Shenfu Qiangxin Pills may exert its efficacy in the treatment of chronic heart failure by regulating the amino acid metabolism.