University of Northern Colorado, Greeley, CO 80639, USA.
Integr Cancer Ther. 2011 Mar;10(1):47-57. doi: 10.1177/1534735410392577. Epub 2011 Mar 7.
Acute doxorubicin (DOX) cardiotoxicity can be attenuated by exercise preconditioning, but little is known of whether this cardioprotection continues beyond 10 days post-DOX administration. The purpose of this study was to determine the effects of exercise preconditioning on early chronic DOX-induced cardiotoxicity. Male rats were randomly assigned to sedentary, treadmill, or wheel running groups. Treadmill and wheel running animals participated in a progressive treadmill training protocol or voluntary wheel running, respectively, for 10 weeks. Following the intervention, animals were further randomized to receive either DOX (sedentary + DOX, treadmill + DOX, wheel running + DOX) or saline (sedentary + saline, treadmill + saline, wheel running + saline). All animals then remained sedentary for 4 weeks. A 22% reduction in fractional shortening was observed in left ventricles from previously sedentary animals receiving DOX when compared with sedentary + saline. This degree of decline was not observed in treadmill + DOX and wheel running + DOX. Sedentary + DOX possessed significantly depressed mitral and aortic valve blood flow velocities when compared with sedentary + saline, but these decrements were not observed in treadmill + DOX and wheel running + DOX. Ex vivo analysis revealed that left ventricular developed pressure and maximal rate of pressure development were significantly lower in sedentary + DOX when compared to sedentary + saline. Treadmill and wheel running prior to DOX treatment protected against these decrements. Exercise cardioprotection was associated with preserved myosin heavy chain but not sarcoendoplasmic reticulum Ca(2+) ATPase 2a expression. In conclusion, 10 weeks of prior exercise protected against early chronic DOX cardiotoxicity suggesting that training status may be a determining factor in the degree of late-onset cardiotoxicity experienced by cancer patients undergoing treatment with DOX.
急性阿霉素（DOX）心脏毒性可以通过运动预处理来减轻，但对于 DOX 给药后 10 天是否仍存在这种心脏保护作用知之甚少。本研究的目的是确定运动预处理对早期慢性 DOX 诱导的心脏毒性的影响。雄性大鼠被随机分为久坐、跑步机或轮跑组。跑步机和轮跑动物分别参加了渐进式跑步机训练方案或自愿轮跑，持续 10 周。干预结束后，动物进一步随机分为 DOX 组（久坐+DOX、跑步机+DOX、轮跑+DOX）或盐水组（久坐+盐水、跑步机+盐水、轮跑+盐水）。所有动物随后保持久坐 4 周。与接受 DOX 的久坐+盐水相比，之前久坐的动物的左心室短轴缩短率降低了 22%。在跑步机+DOX 和轮跑+DOX 中没有观察到这种下降。与久坐+盐水相比，久坐+DOX 的二尖瓣和主动脉瓣血流速度明显降低，但在跑步机+DOX 和轮跑+DOX 中没有观察到这种降低。离体分析显示，与久坐+盐水相比，久坐+DOX 的左心室发展压和最大压力发展率明显降低。DOX 治疗前的跑步机和轮跑运动可防止这些降低。运动心脏保护与肌球蛋白重链的保留有关，但与肌浆网 Ca(2+)ATP 酶 2a 的表达无关。总之，10 周的运动预处理可预防早期慢性 DOX 心脏毒性，这表明训练状态可能是接受 DOX 治疗的癌症患者发生迟发性心脏毒性程度的决定因素。
