Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress

Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress
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DOI:
10.1007/s10753-016-0438-8
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发表时间:
2016-09
期刊:
影响因子:
5.1
通讯作者:
W. Xiao;Yu Liu;Peijie Chen
W. Xiao;Yu Liu;Peijie Chen
中科院分区:
医学2区
文献类型:
--
作者:
W. Xiao;Yu Liu;Peijie Chen

文献摘要

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肌肉挫伤是运动医学中最常见的肌肉损伤之一。巨噬细胞在骨骼肌再生中起着复杂的作用。然而,巨噬细胞在肌肉挫伤再生中的作用,特别是所涉及的机制仍未完全了解。我们假设巨噬细胞的消耗会损害骨骼肌的再生,而促纤维化因子、炎症和氧化应激可能参与了这一过程。为了验证这些假设,我们构建了肌肉挫伤和巨噬细胞消耗模型,并进行了形态学和基因表达分析。数据显示,巨噬细胞耗竭小鼠挫伤后肌肉形成纤维化瘢痕,且瘢痕恶化。此外,巨噬细胞耗竭显著降低了再生肌纤维的大小。促纤维化因子、炎症因子、趋化因子和氧化应激相关酶在肌肉损伤后显著增加。此外,巨噬细胞耗竭延迟了这些因子的表达。大部分在再生后期仍显著升高。这些结果表明,巨噬细胞耗竭会损害骨骼肌再生,促纤维化因子、炎症和氧化应激可能在这一过程中发挥重要作用。
Muscle contusion is one of the most common muscle injuries in sports medicine. Macrophages play complex roles in the regeneration of skeletal muscle. However, the roles of macrophages, especially the mechanisms involved, in the regeneration of muscle contusion are still not fully understood. We hypothesize that the depletion of macrophages impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may be involved in the process. To test these hypotheses, we constructed a muscle contusion injury and a macrophage depletion model and followed it up with morphological and gene expression analyses. The data showed that fibrotic scars were formed in the muscle of contusion injury, and they deteriorated in the mice of macrophage depletion. Furthermore, the sizes of regenerating myofibers were significantly reduced by macrophage depletion. Pro-fibrotic factors, inflammatory cytokines, chemokines, and oxidative stress-related enzymes increased significantly after muscle injury. Moreover, the expression of these factors was delayed by macrophage depletion. Most of them were still significantly higher in the later stage of regeneration. These results suggest that macrophage depletion impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may play important roles in the process.