Integrative Muscle Biology Laboratory, Exercise Science Department, University of South Carolina, Columbia, South Carolina 29208, USA.
J Appl Physiol (1985). 2010 Oct;109(4):1155-61. doi: 10.1152/japplphysiol.00442.2010. Epub 2010 Jul 22.
Criteria for diagnosing cachexia in adults include unintentional loss in body weight, decreased strength, fatigue, anorexia, and low muscle mass. Cachexia is also associated with systemic inflammation, altered metabolism, and anemia. The Apc(Min/+) mouse is a model of cachexia directly related to intestinal tumor burden and subsequent chronic inflammation. These mice also demonstrate muscle weakness, fatigue, decreased volitional activity, and elevated circulating IL-6 levels. The purpose of this study was to determine the time course of changes in physical activity and their relationship to anemia, muscle apoptosis, and muscle mass and body mass loss during cachexia. A subset of male Apc(Min/+) mice were given access to voluntary activity wheels from 5 to 26 wk of age, while sedentary male Apc(Min/+) mice were housed in cages lacking wheels. At the study's end mice were stratified by cachectic symptoms. Severely cachectic mice had decreased wheel running performance at 15 wk of age, while anemia and body weight loss were not present until 18 wk of age. Severely cachectic mice had lower hemoglobin levels compared with mildly cachectic mice at 13, 18, and 22 wk of age. Severely cachectic mice also demonstrated threefold more BCL2-associated X protein (BAX) protein in the gastrocnemius muscle at 26 wk of age compared with mildly cachectic mice. In sedentary Apc(Min/+) mice at 26 wk of age anemia was present, and markers of apoptosis were induced in severely cachectic muscle. Proapoptotic protein expression was induced in both red and white portions of gastrocnemius muscle as well as in soleus muscle of severely cachectic mice compared with mildly cachectic mice. These data demonstrate that decrements in wheel running performance precede loss of body mass and that inherent muscle oxidative capacity is not protective against muscle apoptosis.
诊断成人恶病质的标准包括非自愿性体重减轻、体力下降、乏力、厌食和肌肉量减少。恶病质还与全身炎症、代谢改变和贫血有关。Apc(Min/+)小鼠是一种与肠道肿瘤负担和随后的慢性炎症直接相关的恶病质模型。这些小鼠还表现出肌肉无力、疲劳、自愿活动减少和循环 IL-6 水平升高。本研究的目的是确定体力活动变化的时间过程及其与贫血、肌肉凋亡、肌肉质量和体重减轻在恶病质中的关系。一部分雄性 Apc(Min/+)小鼠从 5 到 26 周龄时被给予自由活动轮，而不活动的雄性 Apc(Min/+)小鼠被安置在没有轮子的笼子里。在研究结束时，根据恶病质症状对小鼠进行分层。严重恶病质的小鼠在 15 周龄时的轮跑性能下降，而贫血和体重减轻直到 18 周龄才出现。严重恶病质的小鼠在 13、18 和 22 周龄时的血红蛋白水平明显低于轻度恶病质的小鼠。严重恶病质的小鼠在 26 周龄时的比目鱼肌中 BCL2 相关 X 蛋白 (BAX) 蛋白也高出三倍。在 26 周龄时不活动的 Apc(Min/+)小鼠中出现了贫血，并且在严重恶病质的肌肉中诱导了凋亡标志物。与轻度恶病质的小鼠相比，促凋亡蛋白在严重恶病质的小鼠的比目鱼肌和腓肠肌的红色和白色部分以及比目鱼肌中均被诱导表达。这些数据表明，轮跑性能下降先于体重减轻，而内在的肌肉氧化能力不能防止肌肉凋亡。
