Blockade of TNF in vivo using cVlq antibody reduces contractile dysfunction of skeletal muscle in response to eccentric exercise in dystrophic mdx and normal mice
Blockade of TNF in vivo using cVlq antibody reduces contractile dysfunction of skeletal muscle in response to eccentric exercise in dystrophic mdx and normal mice
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DOI：
10.1016/j.nmd.2010.09.013
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发表时间：
2011-02-01
影响因子：
2.8
通讯作者：
Pinniger, G. J.
中科院分区：
文献类型：
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作者：
Piers, A. T.;Lavin, T.;Pinniger, G. J.
本研究评价了促炎细胞因子肿瘤坏死因子（TNF）对mdx小鼠运动诱导的肌肉损伤和随后的肌纤维坏死严重程度的影响。成年mdx和非营养不良性C57小鼠用小鼠特异性TNF抗体cVlq处理，然后在定制的小鼠测力计上进行体内进行的损伤性离心收缩方案。肌肉损伤通过（i）方案后即刻的收缩功能障碍（初始扭矩不足），（ii）48小时后的后续肌纤维坏死来量化。与注射阴性对照抗体（cVaM）的小鼠和未处理的小鼠相比，使用cVlq阻断TNF显著降低mdx和C57小鼠中的收缩功能障碍。此外，cVlq治疗显著减少mdx小鼠中的肌纤维坏死。cVlq降低TNF介导的对运动诱导的肌肉损伤的不良反应的体内证据支持使用靶向抗TNF治疗来降低DMD中功能缺陷和营养不良病理学的严重性。(C)2010 Elsevier BV保留所有权利。
This study evaluated the contribution of the pro-inflammatory cytokine, tumour necrosis factor (TNF) to the severity of exercise-induced muscle damage and subsequent myofibre necrosis in mdx mice. Adult mdx and non-dystrophic C57 mice were treated with the mouse-specific TNF antibody cVlq before undergoing a damaging eccentric contraction protocol performed in vivo on a custom built mouse dynamometer. Muscle damage was quantified by (i) contractile dysfunction (initial torque deficit) immediately after the protocol, (ii) subsequent myofibre necrosis 48 h later. Blockade of TNF using cVlq significantly reduced contractile dysfunction in mdx and C57 mice compared with mice injected with the negative control antibody (cVaM) and un-treated mice. Furthermore, cVlq treatment significantly reduced myofibre necrosis in mdx mice. This in vivo evidence that cVlq reduces the TNF-mediated adverse response to exercise-induced muscle damage supports the use of targeted anti-TNF treatments to reduce the severity of the functional deficit and dystropathology in DMD. (C) 2010 Elsevier B.V. All rights reserved.