Exercise Mitigates Cardiac Doxorubicin Accumulation and Preserves Function in the Rat
Exercise Mitigates Cardiac Doxorubicin Accumulation and Preserves Function in the Rat
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DOI：
10.1097/fjc.0b013e3182982ce0
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发表时间：
2013-09-01
影响因子：
3
通讯作者：
Hayward, Reid
中科院分区：
文献类型：
--
作者：
Jensen, Brock T.;Lien, Chia-Ying;Hayward, Reid
目的：阿霉素(DOX)是一种有效的抗肿瘤药物，具有良好的心脏毒性作用。虽然运动已被证明可以预防DOX的心脏毒性，但缺乏明确和简洁的机制来解释其心脏保护作用。本研究旨在确定运动训练是否能减少心脏DOX的蓄积，从而为解释运动对DOX毒性的心脏保护作用提供可能的机制。方法：将SD大鼠随机分为3个主要实验组：静坐组(n=77)、车轮跑步组(n=65)和跑步机组(n=65)。车轮跑步组和跑步组动物在接受DOX治疗前完成了10周的运动。在最后一次训练后24小时，以10 mg/kg的剂量给药。结果：10周的运动预适应减少了心肌DOX的蓄积，且这种减少与心功能的保存有关。结论：运动对DOX损伤的心脏保护作用可能部分是由于减少了心肌的DOX蓄积。
Purpose:Doxorubicin (DOX) is an effective antineoplastic agent with well-characterized cardiotoxic effects. Although exercise has been shown to protect against DOX cardiotoxicity, a clear and concise mechanism to explain its cardioprotective effects is lacking. The purpose of this study was to determine if exercise training reduces cardiac DOX accumulation, thereby providing a possible mechanism to explain the cardioprotective effects of exercise against DOX toxicity.Methods:Sprague-Dawley rats were randomly assigned to 1 of 3 primary experimental groups: sedentary (n = 77), wheel running (n = 65), or treadmill (n = 65). Animals in wheel running and treadmill groups completed 10 weeks of exercise before DOX treatment. DOX was administered 24 hours after the last training session as a bolus intraperitoneal injection at 10 mg/kg. Subgroups of rats from each primary group were killed at 1, 3, 5, 7, and 9 days after DOX exposure to assess cardiac function and DOX accumulation.Results:Ten weeks of exercise preconditioning reduced myocardial DOX accumulation, and this reduction in accumulation was associated with preserved cardiac function.Conclusions:These data suggest that the cardioprotective effects of exercise against DOX-induced injury may be due, in part, to a reduction in myocardial DOX accumulation.