A single 30 min treadmill exercise session is suitable for 'proof-of concept studies' in adult mdx mice: A comparison of the early consequences of two different treadmill protocols

A single 30 min treadmill exercise session is suitable for 'proof-of concept studies' in adult mdx mice: A comparison of the early consequences of two different treadmill protocols
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DOI:
10.1016/j.nmd.2011.07.008
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发表时间:
2012-02-01
影响因子:
2.8
通讯作者:
Grounds, Miranda
Grounds, Miranda
中科院分区:
医学4区
文献类型:
--
作者:
Radley-Crabb, Hannah;Terrill, Jessica;Grounds, Miranda

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久坐不动的成年mdx小鼠的肌肉病理程度非常低,跑步机运动通常用于增加肌纤维坏死;然而,对跑步机运动(导致肌纤维坏死)的营养不良肌肉和血液的早期事件尚不清楚。本研究详细描述了mdx小鼠跑步机运动的两种标准化方案,并描述了单次30分钟跑步机训练(方案A)或4周(每周两次)跑步机运动(方案B)后分子和细胞事件的变化。两种跑步机方案都增加了肌肉损伤的多个标志物。我们的结论是,一个单一的30分钟的跑步机运动会话是一个足够的,方便快速的筛选试验,并可用于“概念验证”的研究,以评估体内的临床前药物的好处。肌纤维坏死、血清CK和氧化应激(特别是氧化与还原蛋白硫醇的比率)是运动后肌肉损伤的可靠标志物;许多参数显示出较高的生物学变化,包括肌肉中关键炎性细胞因子的mRNA水平变化。对于这些参数,运动后的采样(处死和组织采集)时间至关重要。更精确地了解运动后营养不良肌肉的变化,旨在确定杜氏肌营养不良症的生物标志物和新的潜在治疗药物靶点。(c)2011 Elsevier B. V.保留所有权利。
The extent of muscle pathology in sedentary adult mdx mice is very low and treadmill exercise is often used to increase myofibre necrosis; however, the early events in dystrophic muscle and blood in response to treadmill exercise (leading to myofibre necrosis) are unknown. This study describes in detail two standardised protocols for the treadmill exercise of mdx mice and profiles changes in molecular and cellular events after a single 30 min treadmill session (Protocol A) or after 4 weeks of (twice weekly) treadmill exercise (Protocol B). Both treadmill protocols increased multiple markers of muscle damage. We conclude that a single 30 min treadmill exercise session is a sufficient and conveniently fast screening test and could be used in 'proof-of-concept' studies to evaluate the benefits of pre-clinical drugs in vivo. Myofibre necrosis, blood serum CK and oxidative stress (specifically the ratio of oxidised to reduced protein thiols) are reliable markers of muscle damage after exercise; many parameters demonstrated high biological variation including changes in mRNA levels for key inflammatory cytokines in muscle. The sampling (sacrifice and tissue collection) time after exercise for these parameters is critical. A more precise understanding of the changes in dystrophic muscle after exercise aims to identify biomarkers and new potential therapeutic drug targets for Duchenne Muscular Dystrophy. (c) 2011 Elsevier B.V. All rights reserved.