联合运动对单苦参碱所致肺动脉高压肺动脉及右心有害重构的影响。

IF 3.3 3区 医学 Q1 PHYSIOLOGY
Journal of applied physiology Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI:10.1152/japplphysiol.00379.2024
Luciano Bernardes Leite, Leôncio Lopes Soares, Alexandre Martins Oliveira Portes, Bruna Aparecida Fonseca da Silva, Taís Rodrigues Dias, Thayana Inácia Soares, Mirian Quintão Assis, Luiz Otávio Guimarães-Ervilha, Miguel Araújo Carneiro-Júnior, Pedro Forte, Mariana Machado-Neves, Emily Correna Carlo Reis, Antônio José Natali
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引用次数: 0

摘要

本研究的目的是测试在单氯胆碱(MCT)诱导的肺动脉高压(PAH)发展过程中进行中等强度的联合体育运动训练是否会阻碍大鼠肺和右心有害功能和结构重构的进展。Wistar大鼠注射MCT (60 mg/kg), 24小时后进行联合运动训练:有氧运动(跑步机跑60分钟/天;最大运行速度的60%);和阻力运动(爬垂直梯子-爬15次;最大承载负荷的60%),隔天,每周5天,持续约3周。安乐死后,切除肺和右心室(RV),进行组织学、单个心肌细胞和生化分析。联合运动增加了对体力劳动的耐受性(直到疲劳和相对最大负荷的时间),并防止肺动脉阻力(TA/TE)的增加和RV功能(TAPSE)的降低。此外,在从RV分离的肌细胞中,联合运动保留了收缩幅度,以及收缩和松弛速度,并抑制幅度和最大速度的减少,以达到峰值,并抑制细胞内Ca2+瞬态的衰减。此外,联合运动可避免RV (RV重量、心肌细胞、细胞外基质、胶原蛋白、炎症浸润、细胞外基质)和肺(肺泡和肺泡隔)有害结构重塑。此外,联合运动限制了RV (NO和CP)和肺(CAT、GST和NO)氧化应激。综上所述,应用联合运动方案可以阻止mct诱导的PAH大鼠肺和右心功能和结构有害重构的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Combined exercise hinders the progression of pulmonary and right heart harmful remodeling in monocrotaline-induced pulmonary arterial hypertension.

The aim of this study was to test whether combined physical exercise training of moderate intensity executed during the development of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) hinders the progression of pulmonary and right heart harmful functional and structural remodeling in rats. Wistar rats were injected with MCT (60 mg/kg) and after 24 h were exposed to a combined exercise training program: aerobic exercise (treadmill running-60 min/day; 60% of maximum running speed); and resistance exercise (vertical ladder climbing-15 climbs; 60% of maximum carrying load), on alternate days, 5 days/wk, for ∼3 wk. After euthanasia, the lung and right ventricle (RV) were excised and processed for histological, single myocyte, and biochemical analyses. Combined exercise increased the tolerance to physical effort (time until fatigue and relative maximum load) and prevented increases in pulmonary artery resistance (acceleration time (TA)/ejection time (TE)] and reductions in RV function [tricuspid annular plane systolic excursion (TAPSE)]. Moreover, in myocytes isolated from the RV, combined exercise preserved contraction amplitude, as well as contraction and relaxation velocities, and inhibited reductions in the amplitude and maximum speeds to peak and to decay of the intracellular Ca2+ transient. Furthermore, combined exercise avoided RV (RV weight, cardiomyocyte, extracellular matrix, collagen, inflammatory infiltrate, and extracellular matrix) and lung (pulmonary alveoli and alveolar septum) harmful structural remodeling. In addition, combined exercise restricted RV [nitric oxide (NO) and carbonyl protein (CP)] and lung [catalase (CAT), glutathione S-transferase (GST), and NO] oxidative stress. In conclusion, the applied combined exercise regime hinders the progression of pulmonary and right heart functional and structural harmful remodeling in rats with MCT-induced PAH.NEW & NOTEWORTHY This study reveals that combined exercise improves tolerance to physical effort, prevents increases in pulmonary artery resistance, and conserves the right heart function during the progression of pulmonary arterial hypertension. Our analyses show that combined exercise hinders harmful right ventricular and lung structural remodeling and oxidative stress, which reflects in the maintenance of right ventricular myocytes' contractile function by preserving the intracellular calcium cycling. An attenuated progression of the disease impacts positively on its prognosis.

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来源期刊
CiteScore
6.00
自引率
9.10%
发文量
296
审稿时长
2-4 weeks
期刊介绍: The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.
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