Dysregulated tryptophan metabolism and gut microbiota in chronic hypoxia-induced pulmonary hypertension rats

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2025-08-11 DOI:10.1016/j.jpba.2025.117111

Jinhao Shuai , Sheng He , Yang Wang , Junjie Zhen , Duonan Yu , Mengying Lv

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引用次数: 0

Abstract

Pulmonary hypertension (PH) is a life-threatening disease, mainly caused by pulmonary arterial inflammation and remodeling, which resulted in elevated pulmonary arterial pressure (PAP) and ultimate rightsided heart failure. In the present study, Wistar rats were exposed to hypoxia for four weeks to induce PH. Multiomics approaches integrating 16S rRNA sequencing, untargeted and targeted metabolomics were utilized to identify alterations in gut microbiota and host metabolism associated with hypoxia-induced pulmonary hypertension. Rats exposed to hypoxia for four weeks exhibited the increased right ventricular systolic pressure (RVSP), pulmonary vascular remodeling, right ventricular hypertrophy, gut microbiota dysbiosis and disturbed serum metabolism. Tryptophan-pathway targeted metabolomics showed that chronic hypoxia exposure induced an increase of tryptophan, xanthurenic acid and 3-indoleacetic acid levels and a decrease of kynurenine, nicotinamide and kynurenic acid levels. Our research would offer promising targets for early diagnosis and treatment of PH.

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慢性缺氧肺动脉高压大鼠色氨酸代谢和肠道微生物群失调

肺动脉高压（Pulmonary hypertension， PH）是一种危及生命的疾病，主要由肺动脉炎症和重塑引起，导致肺动脉压（Pulmonary arterial pressure， PAP）升高，最终导致右侧心力衰竭。在本研究中，Wistar大鼠暴露于缺氧环境4周以诱导ph。利用整合16S rRNA测序，非靶向和靶向代谢组学的多组学方法来鉴定与缺氧诱导的肺动脉高压相关的肠道微生物群和宿主代谢的改变。缺氧4周后，大鼠右心室收缩压升高，肺血管重构，右心室肥厚，肠道菌群失调，血清代谢紊乱。色氨酸途径靶向代谢组学显示，慢性缺氧暴露诱导色氨酸、黄嘌呤酸和3-吲哚乙酸水平升高，犬尿氨酸、烟酰胺和犬尿酸水平降低。我们的研究将为PH的早期诊断和治疗提供有希望的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.