Reduced skeletal muscle function is associated with decreased fiber cross-sectional area in the Cy/ plus rat model of progressive kidney disease
Reduced skeletal muscle function is associated with decreased fiber cross-sectional area in the Cy/ plus rat model of progressive kidney disease
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DOI：
10.1093/ndt/gfv352
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发表时间：
2016-02-01
影响因子：
6.1
通讯作者：
Allen, Matthew R.
中科院分区：
文献类型：
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作者：
Organ, Jason M.;Srisuwananukorn, Andrew;Allen, Matthew R.
骨骼肌萎缩和功能受损共同作用于慢性肾脏病(CKD)患者的健康下降，但肌肉质量/力量变化的病理生理学尚不清楚。本研究旨在研究Cy/+自发性进展性CKD大鼠模型的肌肉特性。在25、30和35周龄时，对雄性Cy/+(CKD)大鼠及其未受影响的产仔(NLS)的Leg肌肉功能和血清生化进行了活体检测。实验结束时，对指长伸肌(EDL)和比目鱼肌(SOL)的结构和组织学进行了体外评价。我们验证了CKD动物肌肉功能进行性丧失的假说，这种功能缺陷与肌肉质量和质量的丧失有关。与NL大鼠相比，35周龄CKD大鼠的踝关节背屈最大扭矩显著降低，达到最大扭矩的时间更短，背屈和趾屈的一半松弛时间更长。在25~35周，CKD大鼠的最大背屈扭矩(但不包括足屈扭矩)保持不变，而在NL大鼠中，峰值扭矩增加。EDL和SOL的质量、生理横截面积(CSA)和纤维型(肌球蛋白重链亚型)的比例在CKD和NL之间没有差异。然而，CKD大鼠的EDL在所有类型的纤维中都显示出CSA的减少，而SOL中只有MyHC-1纤维的面积减少。本研究结果表明，在Cy/+CKD大鼠模型中，肌肉功能进行性下降。由于CKD和NL的整体肌肉质量和结构没有差异，但CKD肌肉的单个纤维CSA减少，我们的数据表明，功能下降与肌肉纤维萎缩增加有关。
The combination of skeletal muscle wasting and compromised function plays a role in the health decline commonly observed in chronic kidney disease (CKD) patients, but the pathophysiology of muscle mass/strength changes remains unclear. The purpose of this study was to characterize muscle properties in the Cy/+ rat model of spontaneously progressive CKD.Leg muscle function and serum biochemistry of male Cy/+ (CKD) rats and their nonaffected littermates (NLs) were assessed in vivo at 25, 30 and 35 weeks of age. Architecture and histology of extensor digitorum longus (EDL) and soleus (SOL) muscles were assessed ex vivo at the conclusion of the experiment. We tested the hypothesis that animals with CKD have progressive loss of muscle function, and that this functional deficit is associated with loss of muscle mass and quality.Thirty-five-week-old CKD rats produced significantly lower maximum torque in ankle dorsiflexion and shorter time to maximum torque, and longer half relaxation time in dorsiflexion and plantarflexion compared with NL rats. Peak dorsiflexion torque (but not plantarflexion torque) in CKD remained steady from 25 to 35 weeks, while in NL rats, peak torque increased. Mass, physiologic cross-sectional area (CSA) and fiber-type (myosin heavy chain isoform) proportions of EDL and SOL were not different between CKD and NL. However, the EDL of CKD rats showed reduced CSAs in all fiber types, while only MyHC-1 fibers were decreased in area in the SOL.The results of this study demonstrate that muscle function progressively declines in the Cy/+ rat model of CKD. Because whole muscle mass and architecture do not vary between CKD and NL, but CKD muscles show reduction in individual fiber CSA, our data suggest that the functional decline is related to increased muscle fiber atrophy.