A novel ex vivo protocol to mimic human walking gait: implications for Duchenne muscular dystrophy.
A novel ex vivo protocol to mimic human walking gait: implications for Duchenne muscular dystrophy.
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一种模仿人类步行步态的新型离体方案：对杜氏肌营养不良症的影响。
DOI：
10.1152/japplphysiol.00002.2020
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Grange,RobertW
中科院分区：
文献类型：
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作者：
Bukovec,KatherineE;Hu,Xiao;Borkowski,Matthew;Jeffery,Duane;Blemker,SilviaS;Grange,RobertW
我们开发了一种新的离体小鼠方案来模拟通过肌肉骨骼模拟预测的体内人类比目鱼肌功能，以更好地了解步态期间的偏心收缩，并最终更好地了解它们在杜氏肌营养不良症（DMD）肌肉中的作用。DMD肌肉容易受到偏心损伤，因为蛋白质dystrophin缺失。Themdx小鼠是一种同样缺乏抗肌萎缩蛋白的DMD模型，经常受到离体急性但非生理性偏心损伤方案的影响。与人类在步态期间的离心应力和应变相比，这些急性协议可能过度或低估了离心应力和应变。为了探索这种可能性，使用OpenSim模拟健康人比目鱼肌在单个步行步幅（步态周期）期间的激励、力和长度变化曲线，然后基于肌肉结构测量缩放到离体小鼠比目鱼肌制备。Aurora Scientific，Inc.，软件和701C电刺激器被修改为以恒定频率离散地调节肌肉刺激电压，并精细地控制肌肉长度变化，以产生正确地模仿来自模拟的步态周期的力模式。在一项原理验证研究中，野生型和mdx小鼠的比目鱼肌进行了25个步态周期。适度疲劳是明显的肌肉在第25与第一个步态周期的两种基因型，但都迅速恢复等长力在1分钟内的最后一个周期。这些数据表明离体步态方案耐受良好。更重要的是，该协议提供了一种新的评估工具，以确定对营养不良muscle.NEW和NOTEWORTHY一种新的离体小鼠比目鱼肌协议，模仿缩放的长度变化和兴奋曲线预测的数学模型的人比目鱼肌在步态的影响。开发了一种定制刺激器，该刺激器使创新的肌肉刺激技术能够调制电压，以密切匹配步态期间人类比目鱼肌的兴奋模式。该离体方案提供了对小鼠肌肉中的模拟人体运动的评估，包括离心收缩的分量。
We developed a novel ex vivo mouse protocol to mimic in vivo human soleus muscle function predicted by musculoskeletal simulations to better understand eccentric contractions during gait and ultimately to better understand their effects in Duchenne muscular dystrophy (DMD) muscles. DMD muscles are susceptible to eccentric injury because the protein dystrophin is absent. Themdxmouse, a DMD model that also lacks dystrophin, is often subjected to ex vivo acute but nonphysiological eccentric injury protocols. It is possible these acute protocols either over- or underestimate eccentric stresses and strains compared with those from humans during gait. To explore this possibility, healthy human soleus excitation, force, and length change profiles during a single walking stride (gait cycle) were simulated using OpenSim and then scaled to an ex vivo mouse soleus preparation based on muscle architectural measurements. Aurora Scientific, Inc., software and a 701C electrical stimulator were modified to discretely modulate muscle stimulation voltage at constant frequency and finely control muscle length changes to produce a force pattern that correctly mimicked the gait cycle from simulations. In a proof-of-principle study, wild-type andmdxmice soleus muscles were subjected to 25 gait cycles. Modest fatigue was evident in the muscles at the 25th versus first gait cycle for both genotypes, but both rapidly recovered isometric force within 1 min of the last cycle. These data indicate that the ex vivo gait protocol was well tolerated. More important, this protocol provides a novel assessment tool to determine the effects of physiological eccentric contractions on dystrophic muscle.NEW & NOTEWORTHYA novel ex vivo mouse soleus protocol that mimics scaled length change and excitation profiles predicted by a mathematical model of human soleus during gait is presented. A custom stimulator was developed that enabled an innovative muscle stimulation technique to modulate voltage to closely match the excitation pattern of human soleus during gait. This ex vivo protocol provides assessment of simulated human movement in mouse muscle, including components of eccentric contractions.