Doxorubicin acts through tumor necrosis factor receptor subtype 1 to cause dysfunction of murine skeletal muscle
Doxorubicin acts through tumor necrosis factor receptor subtype 1 to cause dysfunction of murine skeletal muscle
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DOI：
10.1152/japplphysiol.00776.2009
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发表时间：
2009-12-01
影响因子：
3.3
通讯作者：
Reid, Michael B.
中科院分区：
文献类型：
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作者：
Gilliam, Laura A. A.;Ferreira, Leonardo F.;Reid, Michael B.
Gilliam LA，Ferreira LF，布鲁顿JD，Moylan JS，Westerblad H，Clair DK，Reid MB.阿霉素通过肿瘤坏死因子受体亚型1引起小鼠骨骼肌功能障碍。J Appl Physiol 107：1935-1942，2009.首次发表于2009年9月24日; doi：10.1152/japplphysiol.00776.2009。接受阿霉素化疗的癌症患者经历肌肉无力和疲劳。肌肉功能障碍的一种假定介质是肿瘤坏死因子-α（TNF）的增加，TNF是一种通过TNF受体亚型1（TNFR 1）介导肢体肌肉收缩功能障碍的促炎细胞因子。我们的主要假设是全身性阿霉素给药会导致肌无力和疲劳。全身给予阿霉素（20 mg/kg）后72 h，趾长伸肌最大力（EDL; P < 0.01）降低，趾长伸肌疲劳加速（P < 0.01），血清TNF水平升高（P < 0.05）。TNFR 1基因缺陷可防止全身阿霉素引起的比力下降，但对疲劳无保护作用（P < 0.01）。这些结果表明，临床多柔比星浓度破坏肢体肌肉功能的TNFR 1依赖性的方式。
Gilliam LA, Ferreira LF, Bruton JD, Moylan JS, Westerblad H, Clair DK, Reid MB. Doxorubicin acts through tumor necrosis factor receptor subtype 1 to cause dysfunction of murine skeletal muscle. J Appl Physiol 107: 1935-1942, 2009. First published September 24, 2009; doi:10.1152/japplphysiol.00776.2009.-Cancer patients receiving doxorubicin chemotherapy experience both muscle weakness and fatigue. One postulated mediator of the muscle dysfunction is an increase in tumor necrosis factor-alpha (TNF), a proinflammatory cytokine that mediates limb muscle contractile dysfunction through the TNF receptor subtype 1 (TNFR1). Our main hypothesis was that systemic doxorubicin administration would cause muscle weakness and fatigue. Systemic doxorubicin administration (20 mg/kg) depressed maximal force of the extensor digitorum longus (EDL; P < 0.01), accelerated EDL fatigue (P < 0.01), and elevated serum TNF levels (P < 0.05) 72 h postinjection. Genetic TNFR1 deficiency prevented the fall in specific force caused by systemic doxorubicin, without protecting against fatigue (P < 0.01). These results demonstrate that clinical doxorubicin concentrations disrupt limb muscle function in a TNFR1-dependent manner.