Effects of aging on basement membrane of the soleus muscle during recovery following disuse atrophy in rats

Effects of aging on basement membrane of the soleus muscle during recovery following disuse atrophy in rats
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DOI:
10.1016/j.exger.2017.08.014
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发表时间:
2017-11-01
影响因子:
3.9
通讯作者:
Shigeyoshi, Yasufumi
Shigeyoshi, Yasufumi
中科院分区:
医学2区
文献类型:
--
作者:
Kanazawa, Yuji;Ikegami, Keisuke;Shigeyoshi, Yasufumi

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众所周知,衰老会导致肌肉在停用后恢复受损,并增加肌肉对损伤的敏感性。在这里,我们表明,在老年大鼠中,在废弃萎缩后重新负荷,会导致肌肉纤维和支撑肌肉纤维的基底膜(BM)的损伤。将3月龄和20月龄雄性Wistar大鼠分别进行后肢卸载2周,再负重1周。在老年大鼠,比目鱼肌出现坏死和中央核纤维,表明肌肉纤维再生。此外,BM的主要成分IV型胶原的异位免疫反应主要与坏死性外观有关,这表明老年大鼠修复受损的BM的能力受到了损害。此外,在卸载和再负荷后,老年大鼠没有表现出明显的变化,尽管年轻大鼠表现出明显的编码IV型胶原的COL4a1和COL4a2基因的反应。此外,在恢复期,年轻大鼠的蛋白质折叠相关因子基因Hsp47和Sparc mRNA的数量增加,而老年大鼠没有表现出任何明显的变化。综上所述,我们的研究结果提示,老年大鼠卸载后萎缩的肌纤维容易受到重量负荷的影响,而骨髓合成成纤维细胞对重力的反应性减弱是导致老年动物肌肉纤维脆性的原因之一。
Aging is known to lead to the impaired recovery of muscle after disuse as well as the increased susceptibility of the muscle to damage. Here, we show that, in the older rats, reloading after disuse atrophy, causes the damage of the muscle fibers and the basement membrane (BM) that structurally support the muscle fibers. Male Wistar rats of 3-(young) and 20-(older) months of age were subjected to hindlimb-unloading for 2 weeks followed by reloading for a week. In the older rats, the soleus muscles showed necrosis and central nuclei fiber indicating the regeneration of muscle fibers. Furthermore, ectopic immunoreactivity of collagen IV, a major component of the BM, remained mostly associated with the necrotic appearance, suggesting that the older rats were impaired with the ability of repairing the damaged BM. Further, after unloading and reloading, the older rats did not show a significant alteration, although the young rats showed clear response of Col4a1 and Col4a2 genes, both coding for collagen IV. In addition, during the recovery phase, the young rats showed increase in the amount of Hsp47 and Sparc mRNA, which are protein folding-related factor genes, while the older rats did not show any significant variation. Taken together, our findings suggest that the atrophic muscle fibers of the older rats induced by unloading were vulnerable to the weight loading, and that attenuated reactivity of the BM-synthesizing fibroblast to gravity contributes to the fragility of muscle fibers in the older animals.