After skeletal muscle injury, unloading disturbs the regenerative process of injured myofibers, in a manner highly attributed to impairment of macrophage functions. However, the effect of unloading on the spatiotemporal context of proinflammatory macrophage recruitment and satellite cell accumulation within the damaged area remains unclear. This study focused on macrophages expressing inducible nitric oxide synthase (iNOS) that synthesize nitric oxide, a key regulator of muscle regeneration, and compared the continuous hindlimb unloading (HU) by tail suspension versus weight-bearing (WB) after skeletal muscle crush injury in rats. We found that in the WB group, the recruitment of iNOS⁺ proinflammatory macrophages into the injured site gradually increased until their peak number at 48 h post-injury. In the HU group, the accumulation of iNOS⁺ macrophages until 48 h after injury was significantly less than that in the WB group and continued to increase at 72 h. In accordance with attenuated and/or delayed iNOS⁺ macrophage recruitment, whole iNOS expression at 24 and 48 h after injury was weakened by unloading. Additionally, in the HU group, satellite cell content of dystrophin-positive non-injured areas diminished at 48 h after injury, and the numbers of activated satellite cells within the regenerating area at 72 and 96 h post-injury were significantly smaller than those in the WB group. These findings suggest that muscle regeneration under unloading conditions results in attenuated and/or delayed recruitment of iNOS⁺ macrophages and lower iNOS expression in the early phase after muscle injury, leading to perturbed satellite cell accumulation and muscle regeneration.

骨骼肌损伤后，卸载扰乱了受损肌纤维的再生过程，这在很大程度上归因于巨噬细胞功能的损害。然而，卸载对受损区域内促炎巨噬细胞募集和卫星细胞积累的时空背景的影响尚不清楚。本研究的重点是表达诱导型一氧化氮合酶 (iNOS) 的巨噬细胞，该酶合成一氧化氮，这是肌肉再生的关键调节剂，并比较了骨骼肌挤压伤后通过尾悬吊与负重 (WB)进行的连续后肢卸载 (HU) 。老鼠。我们发现在WB组中，iNOS ⁺的招募进入受伤部位的促炎巨噬细胞逐渐增加，直到它们在受伤后 48 小时达到峰值。在HU组，iNOS ⁺巨噬细胞在伤后48小时的积累明显少于WB组，并在72小时后继续增加。根据减弱和/或延迟的 iNOS ⁺巨噬细胞募集，损伤后 24 和 48 小时的整个 iNOS 表达因卸载而减弱。此外，HU组肌营养不良蛋白阳性非损伤区卫星细胞含量在伤后48小时减少，伤后72和96小时再生区内活化的卫星细胞数量明显少于伤后48小时。 WB组。这些发现表明，卸载条件下的肌肉再生会导致 iNOS ⁺巨噬细胞的募集减弱和/或延迟，并在肌肉损伤后的早期阶段降低 iNOS 表达，从而导致卫星细胞积累和肌肉再生受到干扰。