Screening of Metabolic Markers of Qi‐Yin deficiency in Chronic Heart Failure Mice by Untargeted Metabolomics Method

Abstract

Qi‐Yin deficiency is the main syndrome of chronic heart failure that one of the major heart disease that threatening human health. Clarifying the time‐history of Qi‐Yin deficiency in chronic heart failure disease, and further exploring the metabolic markers of Qi‐Yin deficiency can help to explain the pathological mechanism and Precise treatment of Qi‐Yin deficiency in chronic heart failure. This study adopted chronic heart failure model induced by coronary artery ligation in mice. We investigated the changes in the appearance of clinical indications corresponding to symptoms of Qi‐Yin deficiency at different time points, which aimed to clear the time‐history of Qi‐Yin deficiency appeared in chronic heart failure model mice. Positive (Yiqifumai) and negative (Danhong) control group were set up to assistant define the time‐history of Qi‐Yin deficiency. We found that Chronic heart failure mice appeared significant weight loss, decreased food intake, spontaneous activity , accelerated heart rate, and increased T wave amplitude in the first 2–3 weeks after modeling. What's more, Yiqifumai had better effects than Danhong in the improvement of Qi‐Yin deficiency in the first 2–3 weeks, which assistant proved that this period was Qi‐Yin deficiency. The coagulation function test results also suggest that it may turn into blood stasis syndrome around 4–5 weeks. In addition, LC‐MS/MS technology was used to determine the endogenous metabolites in serum and urine of mice on the positive ion mode. The data of accurate molecular weight and fragment ion peak were checked on HMDB database, and the identification methods of PCA and OPLS‐DA were used to analyze the multivariable data. Metabolites of the chronic heart failure model mice during the period of Qi‐Yin deficiency and non Qi‐Yin deficiency were compared to explore specific metabolite groups significant related to Qi‐Yin deficiency. The untargeted metabolomic workflow is showed in Figure 1. The results of metabolomic analysis of serum and urine of model mice showed that metabolites were well‐differentiated between the two groups at 2–3 weeks and 4–5 weeks. 29 significant difference metabolites in serum and 19 significant difference metabolites in urine were identified in this study. Hence, these results demonstrated that ischemia‐induced chronic heart failure may be mainly manifested as Qi‐Yin deficiency syndrome in the first 2–3 weeks, followed by conversion to blood stasis syndrome. Metabolites of chronic heart failure mice also changed as the syndrome transformed.Support or Funding InformationNational Natural Science Foundation of China (NO. 81774150)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.