Respiratory and limb muscle weakness induced by tumor necrosis factor-α -: Involvement of muscle myofilaments
Respiratory and limb muscle weakness induced by tumor necrosis factor-α -: Involvement of muscle myofilaments
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DOI：
10.1164/rccm.2202005
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发表时间：
2002-08-15
影响因子：
24.7
通讯作者：
Westerblad, H
中科院分区：
文献类型：
--
作者：
Reid, MB;Lännergren, J;Westerblad, H
在脓毒症、充血性心力衰竭和其他炎症性疾病中，呼吸和肢体骨骼肌会变得虚弱。一个潜在的肌肉无力的介体是肿瘤坏死因子-α，这是一种细胞因子，可以刺激肌肉萎缩，也可以在没有明显分解代谢的情况下导致收缩功能障碍。本研究针对的是后一种过程。用小鼠的横隔肌和四肢肌(指短屈肌[FDB])标本来测定这些肌肉对肿瘤坏死因子-α的相对敏感性。从FDB分离完整的肌肉纤维，并显微注射Indo-1以测量肌浆钙调节的变化。我们发现，在一定的刺激频率范围内，肿瘤坏死因子-α对横隔膜和FDB的强直力的抑制程度相当。在分离的肌肉纤维中，肿瘤坏死因子-α降低了强直力，而不改变强直性钙瞬变或静息钙水平。我们得出的结论是：(1)肿瘤坏死因子-α对横隔肌和四肢肌的收缩功能有相似的损害作用，(2)肿瘤坏死因子-α通过钝化肌丝对钙激活的反应而降低肌力。
The respiratory and limb skeletal muscles become weakened in sepsis, congestive heart failure, and other inflammatory diseases. A potential mediator of muscle weakness is tumor necrosis factor (TNF)-alpha, a cytokine that can stimulate muscle wasting and also can induce contractile dysfunction without overt catabolism. This study addressed the latter process. Murine diaphragm and limb muscle (flexor digitorum brevis [FDB]) preparations were used to determine the relative sensitivities of these muscles to TNF-alpha. Intact muscle fibers were isolated from FDB and microinjected with indo-1 to measure changes in sarcoplasmic calcium regulation. We found that TNF-alpha depressed tetanic force of the diaphragm and FDB to comparable degrees across a range of stimulus frequencies. In isolated muscle fibers, TNF-alpha decreased tetanic force without altering tetanic calcium transients or resting calcium levels. We conclude that (1) TNF-alpha compromises contractile function of diaphragm and limb muscle similarly, and (2) TNF-alpha decreases force by blunting the response of muscle myofilaments to calcium activation.