School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO 80639, USA.
Anticancer Res. 2009 Nov;29(11):4401-7.
The clinical use of the highly effective chemotherapeutic agent doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. This cardiotoxicity is associated with a cardiac myosin heavy chain (MHC) isoform shift from the alpha isoform to the beta isoform. Exercise prior to DOX treatment has been shown to attenuate the MHC shift associated with DOX, but little is known about the cardioprotective nature of exercise during DOX treatment.
DOX-treated rats were assigned to normal cage activity (sedentary, SED+DOX) or 24-hour voluntary wheel running access (WR+DOX). All animals received weekly 2.5 mg/kg DOX injections for 6 weeks (15 mg/kg cumulative) and hearts were subsequently excised for determination of MHC isoform expression using sodium dodecyl sulfate polyacrylamide gel electrophoresis.
At baseline, WR+DOX rats on average ran 62+/-4 km, and at week 6 ran 30+/-5 km, which was significantly lower than baseline (p<0.05). SED+DOX hearts expressed 57+/-7% of MHC as the alpha-MHC isoform and 43+/-7% as the beta-MHC isoform. WR+DOX hearts expressed 76+/-4% as the alpha-MHC and 24+/-4% as the beta-MHC isoform, which was significantly different from that of SED+DOX (p<0.05).
DOX treatment significantly reduced wheel running activity, but this reduced running distance deemed to be cardioprotective as hearts from WR+DOX rats contained significantly greater levels of the favorable alpha-MHC isoform than SED+DOX.
高效化疗药物阿霉素（DOX）的临床应用受到其剂量依赖性心脏毒性的限制。这种心脏毒性与肌球蛋白重链（MHC）同工型从α同工型向β同工型的转变有关。DOX 治疗前的运动已被证明可以减轻与 DOX 相关的 MHC 转移，但对于 DOX 治疗期间运动的心脏保护特性知之甚少。
DOX 处理的大鼠被分配到正常笼活动（静止，SED+DOX）或 24 小时自愿轮跑（WR+DOX）。所有动物每周接受 2.5mg/kg DOX 注射 6 周（累积 15mg/kg），随后切除心脏，使用十二烷基硫酸钠聚丙烯酰胺凝胶电泳测定 MHC 同工型表达。
在基线时，WR+DOX 大鼠平均跑 62+/-4 公里，而在第 6 周跑 30+/-5 公里，明显低于基线（p<0.05）。SED+DOX 心脏表达 57+/-7%的 MHC 为α-MHC 同工型，43+/-7%为β-MHC 同工型。WR+DOX 心脏表达 76+/-4%的α-MHC 和 24+/-4%的β-MHC 同工型，与 SED+DOX 明显不同（p<0.05）。
DOX 治疗显著降低了轮跑活动，但这种减少的跑步距离被认为是心脏保护的，因为 WR+DOX 大鼠的心脏含有明显更高水平的有利的α-MHC 同工型，而不是 SED+DOX。
