High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats
High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats
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DOI：
10.1152/japplphysiol.00957.2015
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发表时间：
2016-05-01
影响因子：
3.3
通讯作者：
Rivero, Jose-Luis L.
中科院分区：
文献类型：
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作者：
Acevedo, Luz M.;Lopez, Ignacio;Rivero, Jose-Luis L.
虽然矿物质代谢和骨骼肌紊乱在慢性肾脏病（CKD）中很常见，但它们之间的潜在关系尚未探讨。血浆磷酸盐、甲状旁腺激素和成纤维细胞生长因子23升高以及骨化三醇水平降低是CKD的常见特征。高磷酸盐摄入是CKD进展的主要原因。本研究的主要目的是确定高磷酸盐摄入对肌肉的影响，并调查钙三醇补充剂是否抵消与长期尿毒症相关的骨骼肌负性变化。在尿毒症大鼠（5/6肾切除术，Nx）的慢收缩比目鱼肌和快收缩胫前肌中评估肌球蛋白为基础的肌纤维类型的比例和代谢及形态学特征，并与假手术（So）对照组进行比较。三组Nx大鼠接受标准饮食（0.6%磷，Nx-Sd）、高磷饮食（0.9%磷，Nx-Pho）或高磷饮食加骨化三醇（10 ng/kg，3天/周ip，Nx-Pho + Cal）12周。两组So大鼠在同一时期接受标准饮食或高磷饮食（So-Pho）。一项涵盖所有纤维类型特征的多变量分析表明，Nx-Pho + Cal大鼠显示出介于Nx-Pho和So-Pho大鼠之间的骨骼肌表型，并且Nx-Pho大鼠中尿毒症诱导的骨骼肌变化幅度大于Nx-Sd大鼠。在尿毒症大鼠中，用骨化三醇治疗保留了肌纤维的纤维类型组成、横截面尺寸、肌纤维结构域尺寸、氧化能力和毛细血管作用。这些数据表明，高磷饮食增强和低剂量骨化三醇减弱长期尿毒症大鼠骨骼肌的不良变化。
Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats.