A 1H NMR spectroscopic metabolomic study of the protective effects of irbesartan in a rat model of chronic mountain sickness

• Published in: Journal of pharmaceutical and biomedical analysis 2021-09, Vol.204, p.114235-114235, Article 114235
• Main Authors: Nijiati, Yiliyaer, Shan, Lianlian, Yang, Tao, Yizibula, Maiwulanijiang, Aikemu, Ainiwaer
• Format: Article
• Language: English
• Subjects: Chronic Mountain Sickness; Irbesartan; Lung tissue; Metabolomics
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2021.114235

•This is the first study of serum metabolites of CMS and treated with irbesartan.•Irbesartan may be a potential therapeutic agent for CMS.•Lung injury in rat was revealed by microstructural and ultrastructural changes.•Amino acid synthesis and energy metabolism play crucial roles in CMS. Chronic mountain sickness (CMS) is a significant pathology in most high-altitude regions globally, affecting the cardiopulmonary system and its mechanism is largely unknown. A metabonomic approach using 1H nuclear magnetic resonance spectroscopy allows for detecting differential metabolites, which provides a global view and mechanisms during CMS development. In this study, we simulated a high-altitude environment to establish a rat model of CMS. Irbesartan was administered to CMS rats at three doses (6.75, 13.5, and 27 mg/kg) once a day for 15 days. HE staining and transmission electron microscopy were used to evaluate the effect of changes on the lung. Based on 1H NMR spectra obtained from serum samples, partial least squares-discriminant analysis (PLS-DA) and its variant orthogonal PLS-DA (OPLS-DA) models were applied to distinguish the different groups. Histopathological sections showed that the alveolar structure was abnormal, inflammatory infiltration occurred in CMS rats, and CMS induced notable metabolic disorder according to the 1H NMR result. However, irbesartan reversed the imbalanced metabolites via energy metabolism, amino acid metabolism, and taurine metabolism pathways, and its effect was also confirmed by the general signs and morphology of the lung. The results revealed that irbesartan as an effective therapeutic agent to improve CMS is warranted.