Hydock David S, Lien Chia-Ying, Schneider Carole M, Hayward Reid
School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO 80639, USA.
Med Sci Sports Exerc. 2008 May;40(5):808-17. doi: 10.1249/MSS.0b013e318163744a.
The clinical use of the chemotherapeutic drug doxorubicin (DOX) is limited due to a dose-dependent cardiotoxicity. Evidence is mounting that exercise protects against DOX-related cardiac dysfunction, and as such, it may be possible that prior endurance training promotes defense against DOX cardiotoxicity.
To examine the effects of exercise preconditioning on acute DOX-induced cardiotoxicity, and to determine whether any observed cardioprotection was associated with myosin heavy chain (MHC) isoform alterations.
Male Sprague-Dawley rats trained on a motorized treadmill, had access to voluntary running wheels, or remained sedentary for 10 wk prior to being injected with either saline or 10 mg.kg(-1) DOX. Left ventricular function was then assessed in vivo using transthoracic echocardiography and ex vivo using the isolated working heart at 5 and 10 d after injection. Additionally, left ventricular MHC isoform expression was analyzed as a possible mechanism to explain exercise-induced cardioprotection.
DOX treatment promoted significant in vivo and ex vivo cardiac dysfunction at 5 and 10 d after injection in sedentary animals, and this dysfunction was associated with an upregulation of the beta-MHC isoform. Exercise preconditioning protected against DOX-induced cardiac dysfunction at 5 and 10 d after injection by attenuating beta-MHC upregulation.
Endurance training prior to DOX treatment protects against acute DOX cardiotoxicity for up to 10 d, and this protection can potentially be explained by a preservation of MHC isoform distribution.
化疗药物阿霉素（DOX）的临床应用因剂量依赖性心脏毒性而受到限制。越来越多的证据表明运动可预防与DOX相关的心脏功能障碍，因此，预先进行耐力训练可能会增强对DOX心脏毒性的防御能力。
研究运动预处理对急性DOX诱导的心脏毒性的影响，并确定观察到的任何心脏保护作用是否与肌球蛋白重链（MHC）亚型改变有关。
雄性Sprague-Dawley大鼠在电动跑步机上训练，可使用自愿跑步轮，或在注射生理盐水或10mg.kg（-1）DOX前久坐10周。然后在注射后5天和10天使用经胸超声心动图在体内评估左心室功能，并使用离体工作心脏在体外评估。此外，分析左心室MHC亚型表达作为解释运动诱导心脏保护作用的可能机制。
在久坐动物中，DOX治疗在注射后5天和10天促进了显著的体内和体外心脏功能障碍，并且这种功能障碍与β-MHC亚型的上调有关。运动预处理通过减弱β-MHC上调来预防注射后5天和10天DOX诱导的心脏功能障碍。
DOX治疗前的耐力训练可预防急性DOX心脏毒性长达10天，这种保护作用可能可以通过MHC亚型分布的保存来解释。
