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运动训练可减少心脏纤维化,促进慢性恰加斯病性心肌病实验模型中心律失常和心脏功能障碍的改善。

Exercise training reduces cardiac fibrosis, promoting improvement in arrhythmias and cardiac dysfunction in an experimental model of chronic chagasic cardiomyopathy.

作者信息

Improta-Caria Alex Cleber, Nonaka Carolina Kymie Vasques, Daltro Pâmela Santana, Azevedo Carine Machado, Barreto Breno Cardim, Carvalho Gisele Batista, Vasconcelos Juliana Fraga, Souza Bruno Solano de Freitas, Macambira Simone Garcia, Soares Milena Botelho Pereira

机构信息

Multicentric Program of Post-Graduate in Biochemistry and Molecular Biology, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil.

Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, Brazil.

出版信息

Front Physiol. 2025 Apr 28;16:1558678. doi: 10.3389/fphys.2025.1558678. eCollection 2025.

Abstract

BACKGROUND

Chagas disease, caused by the parasite , is associated with inflammation and fibrosis, which characterizes chronic Chagasic cardiomyopathy (CCC). CCC manifests as arrhythmias, hypertrophy or dilation of the left ventricle, and it may progress to heart failure. Therefore, interventions are needed to slow the progression of CCC. Aims: We investigated the effects of exercise training in an animal model of CCC.

METHODS

C57BL/6 mice infected with were submitted to a progressively treadmill exercise training protocol. The cardiac function was evaluated by echocardiogram and electrocardiogram. RT-qPCR and morphometric analyses were performed on samples of cardiac tissue to quantify inflammation and fibrosis.

RESULTS

EKG analysis confirmed that all infected mice developed arrhythmias, with different degrees of severity. Exercise improved arrhythmias in 43.75% of chagasic trained mice, and the remaining mice did not show any alteration in EKG. The untrained chagasic group had no improvement in arrhythmias. The ventricular compliance in chagasic trained mice increased, as revealed by the reduction in isovolumetric relaxation time when compared to untrained mice. Exercise induced the reduction of gene expression of TGF-β, TNF-α, IL-1β, IL-6 and MMP-9 and reduced fibrosis in the heart tissue of chagasic mice.

CONCLUSION

Exercise reduced fibrosis in the heart and skeletal muscle, favoring the improvement of arrhythmias, and augment of cardiac complacency in mice with CCC, in addition to decreasing the expression of profibrotic and proinflammatory genes in the heart.

摘要

背景

恰加斯病由寄生虫引起,与炎症和纤维化相关,这是慢性恰加斯性心肌病(CCC)的特征。CCC表现为心律失常、左心室肥厚或扩张,并可能进展为心力衰竭。因此,需要采取干预措施来减缓CCC的进展。目的:我们研究了运动训练在CCC动物模型中的作用。

方法

将感染 的C57BL/6小鼠纳入逐渐增加强度的跑步机运动训练方案。通过超声心动图和心电图评估心脏功能。对心脏组织样本进行RT-qPCR和形态计量分析,以量化炎症和纤维化。

结果

心电图分析证实,所有感染小鼠均出现心律失常,严重程度不同。运动使43.75%的接受训练的恰加斯病小鼠的心律失常得到改善,其余小鼠的心电图未显示任何变化。未接受训练的恰加斯病组心律失常无改善。与未接受训练的小鼠相比,接受训练的恰加斯病小鼠的心室顺应性增加,这通过等容舒张时间的缩短得以体现。运动导致恰加斯病小鼠心脏组织中TGF-β、TNF-α、IL-1β、IL-6和MMP-9的基因表达降低,并减少了纤维化。

结论

运动减少了心脏和骨骼肌的纤维化,有利于改善心律失常,增加CCC小鼠的心脏顺应性,此外还降低了心脏中促纤维化和促炎基因的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a6/12066638/7e3edb7f8327/fphys-16-1558678-g001.jpg

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