Samuels S E, Knowles A L, Tilignac T, Debiton E, Madelmont J C, Attaix D
Food, Nutrition and Health, Faculty of Agricultural Sciences, The University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Am J Physiol Regul Integr Comp Physiol. 2001 Jul;281(1):R133-9. doi: 10.1152/ajpregu.2001.281.1.R133.
The influence of cancer cachexia and chemotherapy and subsequent recovery of skeletal muscle protein mass and turnover was investigated in mice. Cancer cachexia was induced using colon 26 adenocarcinoma, which is characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea, cystemustine (C(6)H(12)CIN(3)O(4)S). Reduced food intake was not a factor in these studies. Three days after cachexia began, healthy and tumor-bearing mice were given a single intraperitoneal injection of cystemustine (20 mg/kg). Skeletal muscle mass in tumor-bearing mice was 41% lower (P < 0.05) than in healthy mice 2 wk after cachexia began. Skeletal muscle wasting was mediated initially by decreased protein synthesis (-38%; P < 0.05) and increased degradation (+131%; P < 0.05); later wasting resulted solely from decreased synthesis (~-54 to -69%; P < 0.05). Acute cytotoxicity of chemotherapy did not appear to have an important effect on skeletal muscle protein metabolism in either healthy or tumor-bearing mice. Recovery began 2 days after treatment; skeletal muscle mass was only 11% lower than in healthy mice 11 days after chemotherapy. Recovery of skeletal muscle mass was affected initially by decreased protein degradation (-80%; P < 0.05) and later by increased protein synthesis (+46 to +73%; P < 0.05) in cured compared with healthy mice. This study showed that skeletal muscle wasted from cancer cachexia and after chemotherapeutic treatment is able to generate a strong anabolic response by making powerful changes to protein synthesis and degradation.
在小鼠中研究了癌症恶病质、化疗以及随后骨骼肌蛋白质质量和周转率的恢复情况。使用结肠26腺癌诱导癌症恶病质，该模型具有人类疾病的特征，并且可以使用实验性亚硝基脲——胱胺氮芥（C₆H₁₂CIN₃O₄S）以100%的疗效治愈。食物摄入量减少在这些研究中并非一个因素。恶病质开始三天后，对健康小鼠和荷瘤小鼠进行单次腹腔注射胱胺氮芥（20mg/kg）。恶病质开始2周后，荷瘤小鼠的骨骼肌质量比健康小鼠低41%（P<0.05）。骨骼肌萎缩最初是由蛋白质合成减少（-38%；P<0.05）和降解增加（+131%；P<0.05）介导的；后期萎缩仅由合成减少（~-54%至-69%；P<0.05）导致。化疗的急性细胞毒性似乎对健康小鼠或荷瘤小鼠的骨骼肌蛋白质代谢没有重要影响。治疗后2天开始恢复；化疗后11天，骨骼肌质量仅比健康小鼠低11%。与健康小鼠相比，治愈小鼠骨骼肌质量的恢复最初受蛋白质降解减少（-80%；P<0.05）影响，后期受蛋白质合成增加（+46%至+73%；P<0.05）影响。这项研究表明，因癌症恶病质和化疗而消瘦的骨骼肌能够通过对蛋白质合成和降解进行有力改变来产生强烈的合成代谢反应。
