Zombeck Jonathan A, Fey Edward G, Lyng Gregory D, Sonis Stephen T
Biomodels, Watertown, Massachusetts, USA.
Comp Med. 2013;63(6):491-7.
Fatigue is a debilitating and pervasive complication of cancer and cancer care. Clinical research investigating potential therapies is hindered by variability in patient histories, different metrics for measuring fatigue, and environmental factors that may affect fatigue. The purpose of this study was to establish an animal model of chemotherapy-related fatigue. Female HSD:ICR mice were treated with doxorubicin (2.5 mg/kg) or saline in 2 cycles (days 1 through 3 and 10 through 12). After treatment, mice were individually housed in cages equipped with running wheels. Open-field activity and motor coordination were examined after each cycle of treatment and after each week of wheel running. In a separate cohort, modafinil (50 mg/kg) was assessed as a potential treatment for fatigue. Doxorubicin administration resulted in greater than 30% less wheel running compared with that of saline controls. Activity differences were specific to wheel running: neither distance traveled in the open field nor motor coordination according to the rotarod test differed between groups. Compared with control values, RBC counts in the doxorubicin group were decreased on days 15 and 22 but recovered to control levels by study completion. Modafinil was efficacious in increasing wheel running in the doxorubicin group. The current results establish an animal model of chemotherapy-related fatigue that recapitulates the physical symptoms of cancer-related fatigue as manifested as decreased voluntary activity. This model is sensitive to pharmaceutical intervention and can be used to screen potential treatments for fatigue.
疲劳是癌症及癌症治疗中一种使人衰弱且普遍存在的并发症。研究潜在疗法的临床研究因患者病史的差异、测量疲劳的不同指标以及可能影响疲劳的环境因素而受阻。本研究的目的是建立化疗相关疲劳的动物模型。将雌性HSD:ICR小鼠分为两组，分别用阿霉素（2.5毫克/千克）或生理盐水进行两个周期的治疗（第1天至第3天和第10天至第12天）。治疗后，将小鼠单独饲养在配备有跑步轮的笼子里。在每个治疗周期后以及每周跑步后，检测旷场活动和运动协调性。在另一组实验中，评估莫达非尼（50毫克/千克）作为疲劳潜在治疗药物的效果。与生理盐水对照组相比，阿霉素给药后小鼠跑步轮活动减少超过30%。活动差异仅体现在跑步轮活动上：两组在旷场中行走的距离或根据转棒试验得出的运动协调性并无差异。与对照值相比，阿霉素组在第15天和第22天红细胞计数下降，但在研究结束时恢复到对照水平。莫达非尼可有效增加阿霉素组的跑步轮活动。目前的结果建立了一种化疗相关疲劳的动物模型，该模型概括了癌症相关疲劳的身体症状，表现为自发活动减少。该模型对药物干预敏感，可用于筛选疲劳的潜在治疗方法。
