Mechanics of dystrophin deficient skeletal muscles in very young mice and effects of age.
Mechanics of dystrophin deficient skeletal muscles in very young mice and effects of age.
复制标题
幼年小鼠肌营养不良蛋白缺陷骨骼肌的机制和年龄的影响。
DOI：
10.1152/ajpcell.00155.2019
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Boriek,AladinM
中科院分区：
文献类型：
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作者：
Lopez,MichaelA;Bontiff,Sherina;Adeyeye,Mary;Shaibani,AzizI;Alexander,MatthewS;Wynd,Shari;Boriek,AladinM
MDX小鼠是杜氏肌营养不良症的动物模型，杜氏肌营养不良症是一种人类疾病，其特征是缺乏细胞骨架蛋白——肌营养不良蛋白。我们假设：1)肌营养不良蛋白通过促进被动顺应性、粘弹性和收缩力产生，在骨骼肌中起着复杂的机械作用；2)年龄是MDX小鼠骨骼肌被动力学的调节剂。利用体外双轴力学测试装置，我们测量了肌肉纤维方向和纤维横向的被动长度-张力关系、粘弹性应力-松弛曲线和等距收缩特性。为了避免混淆肌肉坏死、炎症和纤维化的继发性影响，我们使用了非常年轻的3周龄小鼠，其肌肉反映了纤维化前和坏死前状态。与对照组相比，MDX小鼠肌肉沿纤维方向和横向向纤维方向的伸展性和顺应性更大；2)肌营养不良蛋白缺乏的膈肌松弛弹性模量更大。此外，在横纤维被动应力存在和不存在的情况下，等长收缩肌肉应力都减少了。我们还研究了年龄对横膈膜长度-张力关系的影响，发现9个月大的MDX小鼠的横膈膜肌肉的柔顺性和可扩展性明显低于非常年轻的MDX小鼠。我们的数据表明，MDX小鼠的年龄是膈肌被动力学的决定因素；在纤维化前/坏死前阶段，肌肉的延伸性和顺应性，以及粘弹性和肌肉收缩性都因肌营养不良蛋白的缺失而改变。
The MDX mouse is an animal model of Duchenne muscular dystrophy, a human disease marked by an absence of the cytoskeletal protein, dystrophin. We hypothesized that1) dystrophin serves a complex mechanical role in skeletal muscles by contributing to passive compliance, viscoelastic properties, and contractile force production and2) age is a modulator of passive mechanics of skeletal muscles of the MDX mouse. Using an in vitro biaxial mechanical testing apparatus, we measured passive length-tension relationships in the muscle fiber direction as well as transverse to the fibers, viscoelastic stress-relaxation curves, and isometric contractile properties. To avoid confounding secondary effects of muscle necrosis, inflammation, and fibrosis, we used very young 3-wk-old mice whose muscles reflected the prefibrotic and prenecrotic state. Compared with controls,1) muscle extensibility and compliance were greater in both along fiber direction and transverse to fiber direction in MDX mice and2) the relaxed elastic modulus was greater in dystrophin-deficient diaphragms. Furthermore, isometric contractile muscle stress was reduced in the presence and absence of transverse fiber passive stress. We also examined the effect of age on the diaphragm length-tension relationships and found that diaphragm muscles from 9-mo-old MDX mice were significantly less compliant and less extensible than those of muscles from very young MDX mice. Our data suggest that the age of the MDX mouse is a determinant of the passive mechanics of the diaphragm; in the prefibrotic/prenecrotic stage, muscle extensibility and compliance, as well as viscoelasticity, and muscle contractility are altered by loss of dystrophin.