Chicco Adam J, Hydock David S, Schneider Carole M, Hayward Reid
School of Sport and Exercise Science, Univ. of Northern Colorado, Greeley, CO 80639, USA.
J Appl Physiol (1985). 2006 Feb;100(2):519-27. doi: 10.1152/japplphysiol.00148.2005. Epub 2005 Oct 6.
Doxorubicin (Dox) is a highly effective antineoplastic antibiotic associated with a dose-limiting cardiotoxicity that may result in irreversible cardiomyopathy and heart failure. The purpose of this study was to examine the effects of low-intensity exercise training (LIET) during the course of Dox treatment on cardiac function, myosin heavy chain expression, oxidative stress, and apoptosis activation following treatment. Male Sprague-Dawley rats either remained sedentary or were exercise trained on a motorized treadmill at 15 m/min, 20 min/day, 5 days/wk (Monday through Friday) for 2 wk. During the same 2-wk period, Dox (2.5 mg/kg) or saline was administered intraperitoneally to sedentary and exercised rats 3 days/wk (Monday, Wednesday, Friday) 1-2 h following the exercise training sessions (cumulative Dox dose: 15 mg/kg). Five days following the final injections, hearts were isolated for determination of left ventricular (LV) function, lipid peroxidation, antioxidant enzyme protein expression, 72-kDa heat shock protein expression, caspase-3 activity, and myosin heavy chain isoform expression. Dox treatment significantly impaired LV function and increased caspase-3 activity in sedentary animals (P < 0.05). LIET attenuated the LV dysfunction and apoptotic signal activation induced by Dox treatment and increased glutathione peroxidase expression, but it had no significant effect on lipid peroxidation, protein expression of myosin heavy chain isoforms, 72-kDa heat shock protein, or superoxide dismutase isoforms. In conclusion, our data suggest that LIET applied during chronic Dox treatment protects against cardiac dysfunction following treatment, possibly by enhancing antioxidant defenses and inhibiting apoptosis.
阿霉素（Dox）是一种高效的抗肿瘤抗生素，具有剂量限制性心脏毒性，可能导致不可逆的心肌病和心力衰竭。本研究的目的是检测在Dox治疗过程中进行低强度运动训练（LIET）对治疗后心脏功能、肌球蛋白重链表达、氧化应激和凋亡激活的影响。雄性Sprague-Dawley大鼠要么保持 sedentary，要么在电动跑步机上以15米/分钟的速度、每天20分钟、每周5天（周一至周五）进行2周的运动训练。在相同的2周期间，在运动训练课程后1-2小时，每周3天（周一、周三、周五）对 sedentary 和运动训练的大鼠腹腔注射Dox（2.5毫克/千克）或生理盐水（累积Dox剂量：15毫克/千克）。最后一次注射后5天，分离心脏以测定左心室（LV）功能、脂质过氧化、抗氧化酶蛋白表达、72-kDa热休克蛋白表达、半胱天冬酶-3活性和肌球蛋白重链异构体表达。Dox治疗显著损害了 sedentary 动物的LV功能并增加了半胱天冬酶-3活性（P < 0.05）。LIET减轻了Dox治疗诱导的LV功能障碍和凋亡信号激活，并增加了谷胱甘肽过氧化物酶表达，但对脂质过氧化、肌球蛋白重链异构体的蛋白表达、72-kDa热休克蛋白或超氧化物歧化酶异构体没有显著影响。总之，我们的数据表明，在慢性Dox治疗期间应用LIET可预防治疗后的心脏功能障碍，可能是通过增强抗氧化防御和抑制凋亡来实现的。
