Eens Sander, Favere Kasper, Van Hecke Manon, Van den Bogaert Siel, Fransen Erik, Roskams Tania, Guns Pieter-Jan, Heidbuchel Hein
Research Group Cardiovascular Diseases, GENCOR, University of Antwerp, Universiteitsplein 1, Antwerp, 2610, Belgium.
Laboratory of Physiopharmacology, GENCOR, University of Antwerp, Antwerp, 2610, Belgium.
Sci Rep. 2025 Aug 12;15(1):29607. doi: 10.1038/s41598-025-13437-x.
Athletes often exhibit unexplained non-ischemic myocardial fibrosis, which is associated with malignant arrhythmias. Given the prevalent (over)use of NSAIDs among athletes and their harmful effects during viral myocarditis, this study examined the effects of combined NSAIDs and endurance exercise on the disease progression. To this end, male C57BL/6J mice underwent eight weeks of treadmill running (60 min/day; 18 cm/s) or no exercise. After two weeks, mice were implanted with mini-pumps delivering ibuprofen (70 mg/kg bw/day) or vehicle. Myocarditis was induced via intraperitoneal coxsackievirus inoculation. Mice were sacrificed six weeks post-inoculation for ventricular arrhythmogenicity evaluation and cardiac histopathological and molecular analysis. Exercising coxsackievirus-infected mice receiving ibuprofen recovered faster from weight loss. Mortality was low and similar across groups. Histopathology revealed abating inflammation and cell loss, without significant group differences. While exercise tended to increase extensive myocardial fibrosis, statistical analyses indicated no significant differences-with or without NSAIDs-in perivascular fibrosis, interstitial fibrosis, or myocardial scarring. NSAIDs-irrespective of exercise-did not increase arrhythmogenicity. In conclusion, ibuprofen in exercising mice with viral myocarditis resulted in faster weight loss recovery, without significant differences in inflammation, fibrosis, or arrhythmogenesis compared to exercise-only mice.
运动员常表现出不明原因的非缺血性心肌纤维化，这与恶性心律失常有关。鉴于非甾体抗炎药在运动员中普遍（过度）使用及其在病毒性心肌炎期间的有害影响，本研究考察了非甾体抗炎药与耐力运动联合使用对疾病进展的影响。为此，雄性C57BL/6J小鼠进行了为期八周的跑步机跑步（每天60分钟；速度18厘米/秒）或不运动。两周后，给小鼠植入输送布洛芬（70毫克/千克体重/天）或赋形剂的微型泵。通过腹腔接种柯萨奇病毒诱导心肌炎。接种六周后处死小鼠，进行室性心律失常评估以及心脏组织病理学和分子分析。接受布洛芬治疗的运动型柯萨奇病毒感染小鼠体重减轻恢复更快。各实验组死亡率较低且相似。组织病理学显示炎症和细胞损失减轻，各实验组之间无显著差异。虽然运动往往会增加广泛的心肌纤维化，但统计分析表明，无论是否使用非甾体抗炎药，血管周围纤维化、间质纤维化或心肌瘢痕形成均无显著差异。无论是否运动，非甾体抗炎药均不会增加心律失常的发生率。总之，在患有病毒性心肌炎的运动小鼠中，布洛芬可使体重减轻恢复更快，与仅运动的小鼠相比，在炎症、纤维化或心律失常发生方面无显著差异。
