School of Sport and Exercise Science and the Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO.
J Cardiovasc Pharmacol. 2013 Oct;62(4):355-60. doi: 10.1097/FJC.0b013e31829c9993.
Doxorubicin (DOX) is a highly effective anthracycline antibiotic used to treat a wide array of cancers. Its use is limited because of dose-dependent cardiovascular toxicity. Although exercise training has been shown to protect against DOX-induced cardiotoxicity, it is unclear as to whether exercise can attenuate DOX-induced vascular dysfunction. The purpose of this study was to determine if exercise training provides protection against the deleterious vascular effects of DOX treatment and if any changes in vascular function are related to the accumulation of DOX in vascular tissue. Male Sprague-Dawley rats remained sedentary (SED) or engaged in 14 weeks of voluntary wheel running (WR). After the 14-week period, animals received 15 mg DOX per kilogram of body mass or an equivalent volume of saline. Twenty-four hours after DOX/saline exposure, the aorta was isolated and was used to examine vascular function and aortic DOX accumulation. Aortic rings from WR + DOX animals contracted with significantly greater force and showed improved endothelium-independent relaxation when compared with rings from SED + DOX animals. In contrast, no significant differences in endothelium-dependent aortic function were noted between WR + DOX and SED + DOX. Furthermore, no significant differences in aortic DOX accumulation were observed between the DOX groups. These results suggest that chronic exercise attenuates vascular smooth muscle dysfunction associated with DOX treatment and seems to be independent of DOX accumulation in vascular tissue.
多柔比星（DOX）是一种高效的蒽环类抗生素，用于治疗多种癌症。由于剂量依赖性的心血管毒性，其应用受到限制。尽管运动训练已被证明可以预防 DOX 引起的心脏毒性，但运动是否可以减轻 DOX 引起的血管功能障碍仍不清楚。本研究的目的是确定运动训练是否可以防止 DOX 治疗的有害血管作用，以及血管功能的任何变化是否与 DOX 在血管组织中的积累有关。雄性 Sprague-Dawley 大鼠保持久坐（SED）或进行 14 周的自愿轮跑（WR）。14 周后，动物接受 15mg/kg 体重的 DOX 或等量生理盐水。在 DOX/生理盐水暴露 24 小时后，分离主动脉并用于检查血管功能和主动脉 DOX 积累。与 SED+DOX 组的血管环相比，WR+DOX 动物的血管环收缩力显著增加，并且表现出改善的非依赖性内皮舒张功能。相比之下，WR+DOX 和 SED+DOX 组之间没有观察到内皮依赖性主动脉功能的显著差异。此外，两组 DOX 组之间主动脉 DOX 积累没有明显差异。这些结果表明，慢性运动可减轻与 DOX 治疗相关的血管平滑肌功能障碍，并且似乎与 DOX 在血管组织中的积累无关。
