Targeted Plasma Amino Acid Metabolic Remodeling and Pharmacological Regulation in Heart Failure Rats Using PRISE-NUS-bs-HSQC 2D NMR Spectroscopy.

摘要

Nuclear magnetic resonance (NMR) metabolomics offers a robust platform for the analysis of complex biological samples, but its application is often constrained by signal overlap and limited sensitivity. In this study, we developed an optimized two-dimensional NMR approach (probe-induced sensitivity enhancement with nonuniform sampling and band-selective 1H-13C HSQC [PRISE-NUS-bs-HSQC]) to enable high-throughput, high-resolution semiquantitative profiling of 22 amino acids in plasma from a rat model of heart failure (HF). When combined with spatially resolved metabolomics of cardiac tissue using AFADESI-MSI, plasma levels of valine, leucine, isoleucine, phenylalanine, methionine, and glutamine showed positive correlations with metabolic disturbances in the infarct (I) area of the heart. A composite biomarker panel derived from these amino acids distinguished HF rats from controls with an area under the curve (AUC) of 0.926. Using multiple therapeutic strategies, including traditional Chinese medicine (TCM), Western medicine, combined therapy with TCM and Western medicine, and active ingredients from Chinese medicine, we observed that all interventions reversed HF-associated amino acid metabolic dysregulation to varying extents. Notably, combined treatment with Qishen Yiqi dropping pills and sacubitril/valsartan produced broader metabolic normalization and more pronounced synergistic effects than either monotherapy. Collectively, this study establishes a noninvasive and efficient 2D NMR-based framework for exploring the association between systemic amino acid metabolism and regional cardiac injury in HF. The integrated analytical strategy provides mechanistic insight into amino acid metabolic remodeling during HF progression and underscores its translational potential for noninvasive diagnosis and therapeutic evaluation.