Huang Sheng-Chih, Wu Jin-Fu, Saovieng Suchada, Chien Wei-Horng, Hsu Ming-Fen, Li Xiao-Fei, Lee Shin-Da, Huang Chih-Yang, Huang Chih-Yang, Kuo Chia-Hua
Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.
Graduate Institute of Physical Therapy and Rehabilitation Science, China Medical University, Taichung, Taiwan.
J Cachexia Sarcopenia Muscle. 2017 Apr;8(2):277-284. doi: 10.1002/jcsm.12148. Epub 2016 Oct 10.
Doxorubicin, a widely used anti-tumour drug, is known to cause muscle loss in cancer patients.
Following an acute dose of doxorubicin injection (2.5 mg/kg per body weight), we examined macrophage distribution in rat soleus muscle challenged by eccentric exercise (downhill running). Long-term doxorubicin treatment (one injection every 3 days) on muscle mass and survival were also determined.
Under non-exercised condition, increased tumour necrosis factor (TNF)-alpha mRNA and decreased IL-10 mRNA were observed in soleus muscle of doxorubicin-treated rats, compared with saline-treated control rats. However, increases in inflammation score (leukocyte infiltration), nitrotyrosine level, and M1 macrophage (CD68 ) invasion in exercised soleus muscle were absent in doxorubicin-treated rats, whereas increased M2 macrophage (CD163 ) localization in exercised muscle was less affected by doxorubicin. Despites coenzyme Q (Q10) supplementation significantly elevated TNF-alpha mRNA, nitrotyrosine, and anti-oxidant gamma-glutamylcysteine synthetase (GCS) levels in non-exercised soleus muscle, these pro-inflammatory responses were also abolished in doxorubicin-treated rats. Results from long-term doxorubicin treatment show a significant muscle loss followed by an accelerated death, which cannot be reversed by Q10 supplementation.
(i) Doxorubicin impairs inflammation mechanism by depleting M1 macrophage in exercised skeletal muscle; (ii) Muscle loss and accelerated death during prolonged doxorubicin treatment cannot be reversed by Q10 supplementation.
阿霉素是一种广泛使用的抗肿瘤药物，已知会导致癌症患者肌肉流失。
在急性注射一剂阿霉素（2.5毫克/千克体重）后，我们检测了受离心运动（下坡跑）挑战的大鼠比目鱼肌中巨噬细胞的分布情况。还测定了阿霉素长期治疗（每3天注射一次）对肌肉质量和存活率的影响。
在非运动条件下，与生理盐水处理的对照大鼠相比，阿霉素处理的大鼠比目鱼肌中肿瘤坏死因子（TNF）-α mRNA增加，白细胞介素-10 mRNA减少。然而，阿霉素处理的大鼠在运动的比目鱼肌中炎症评分（白细胞浸润）、硝基酪氨酸水平和M1巨噬细胞（CD68）浸润并未增加，而运动肌肉中M2巨噬细胞（CD163）定位的增加受阿霉素的影响较小。尽管补充辅酶Q（Q10）显著提高了非运动比目鱼肌中TNF-α mRNA、硝基酪氨酸和抗氧化剂γ-谷氨酰半胱氨酸合成酶（GCS）的水平，但这些促炎反应在阿霉素处理的大鼠中也被消除了。长期阿霉素治疗的结果显示，肌肉显著流失，随后死亡加速，补充Q10无法逆转这种情况。
（i）阿霉素通过消耗运动骨骼肌中的M1巨噬细胞来损害炎症机制；（ii）长期阿霉素治疗期间的肌肉流失和加速死亡不能通过补充Q10来逆转。
