Non-invasive muscle contraction assay to study rodent models of sarcopenia.

Non-invasive muscle contraction assay to study rodent models of sarcopenia.
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DOI:
10.1186/1471-2474-12-246
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发表时间:
2011-10-28
影响因子:
2.3
通讯作者:
Wilkinson HA
Wilkinson HA
中科院分区:
医学3区
文献类型:
--
作者:
Chiu CS;Weber H;Adamski S;Rauch A;Gentile MA;Alves SE;Kath G;Flores O;Wilkinson HA

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与年龄相关的肌肉减少症是一种肌肉质量和力量丧失的疾病状态,影响身体功能和活动能力,导致跌倒、骨折和残疾。治疗与年龄相关的肌肉减少症的疗法的需求吸引了深入的临床前研究。为了促进这些疗法的发现,我们开发了一种非侵入性大鼠肌肉功能测定系统,以有效测量肌肉力量并评估候选药物的功效。麻醉大鼠的小腿肌肉通过膝盖支架和脚跟支撑上的表面电极进行人工刺激,导致小腿肌肉推动连接到力传感器的等距踏板。我们开发了一种刺激方案来执行疲劳测试,揭示功能性肌肉参数,如最大力、疲劳率、抗疲劳力以及疲劳肌肉力指数。该系统在大鼠衰老模型和大鼠糖皮质激素诱导的肌肉损失模型中进行了评估。老年大鼠通常比成年大鼠更虚弱,并且与抗疲劳力相比,其疲劳力表现出更大的降低。糖皮质激素治疗的大鼠大多失去疲劳力并且疲劳率较高,表明糖酵解纤维的力减少,能量储备减少。无意识收缩测定是评估啮齿动物肌肉功能的可靠系统,可应用于临床前研究,包括与年龄相关的肌少症和其他肌病。
Age-related sarcopenia is a disease state of loss of muscle mass and strength that affects physical function and mobility leading to falls, fractures, and disability. The need for therapies to treat age-related sarcopenia has attracted intensive preclinical research. To facilitate the discovery of these therapies, we have developed a non-invasive rat muscle functional assay system to efficiently measure muscle force and evaluate the efficacy of drug candidates. The lower leg muscles of anesthetized rats are artificially stimulated with surface electrodes on the knee holders and the heel support, causing the lower leg muscles to push isometric pedals that are attached to force transducers. We developed a stimulation protocol to perform a fatigability test that reveals functional muscle parameters like maximal force, the rate of fatigue, fatigue-resistant force, as well as a fatigable muscle force index. The system is evaluated in a rat aging model and a rat glucocorticoid-induced muscle loss model The aged rats were generally weaker than adult rats and showed a greater reduction in their fatigable force when compared to their fatigue-resistant force. Glucocorticoid treated rats mostly lost fatigable force and fatigued at a higher rate, indicating reduced force from glycolytic fibers with reduced energy reserves. The involuntary contraction assay is a reliable system to assess muscle function in rodents and can be applied in preclinical research, including age-related sarcopenia and other myopathy.
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