高血圧における陰虚陽亢症候群患者のガスクロマトグラフィー-質量分析法ベースの血漿メタボロミクス解析

Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases, stroke, and renal failure. Traditional Chinese Medicine (TCM) has been utilized for an extended period to address hypertension, with the syndrome known as Yin deficiency and Yang hyperactivity syndrome (YDYHS) frequently observed in individuals with elevated blood pressure. This syndrome is characterized by symptoms including dizziness, tinnitus, irritability, and insomnia, which are thought to result from an imbalance between Yin, representing the cooling and nourishing aspects, and Yang, denoting the active and warming aspects of the body. Despite the prevalent application of TCM in clinical settings, the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.

To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry (GC-MS) to elucidate the distinctive blood metabolite pattern in this patient population.

GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls. Chemometric methods, including principal component analysis and partial least squares discriminant analysis, were employed to identify potential biochemical patterns. Simultaneously, the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways. Using variable importance in projection and receiver operating characteristic curve analyses, potential biomarkers were extracted to assess their clinical utility.

Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers (4-hydroxybenzoic acid, pectin, 1,2,3-trihydroxybenzene, D-ribose, 3-hydroxybutyric acid, quinic acid, L-lysine, oleic acid, 2-hydroxybutyric acid, linoleic acid, citric acid, alpha-tocopherol, D-glucuronic acid, glycerol, N-acetyl-L-aspartic acid, beta-mannosylglycerate, indolelactic acid, L-glutamic acid, D-maltose, L-aspartic acid) and four metabolic pathways (linoleic acid metabolism; alanine, aspartate and glutamate metabolism; D-glutamine and D-glutamate metabolism; arginine biosynthesis). The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls. The area under the curve values ranged from 0.750 to 0.866. Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.

The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group, highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients. These findings may serve as an important material basis for understanding the occurrence and development of the disease, providing a scientific foundation for future clinical diagnosis.