Xu Miaomiao, Liu Xiaoguang, Bao Peng, Wang Yan Jie, Lu Jianqiang, Liu Yu Jian
School of Kinesiology, Shanghai University of Sport, Shanghai, China.
Guangzhou Sport University Sports and Health, Guangzhou Sport University, Guangzhou, China.
Front Physiol. 2022 Apr 6;13:844539. doi: 10.3389/fphys.2022.844539. eCollection 2022.
Chronic inflammation and oxidative stress are major triggers of the imbalance between protein synthesis and degradation during the pathogenesis of immobilization-induced muscle atrophy. This study aimed to elucidate the effects of hydrogen sulfide (HS), a gas transmitter with potent anti-inflammatory and antioxidant properties, on immobilization-induced muscle atrophy. Mice were allocated to control and immobilization (IM) groups, which were treated with slow (GYY4137) or rapid (NaHS) HS releasing donors for 14 days. The results showed that both GYY4137 and NaHS treatment reduced the IM-induced muscle loss, and increased muscle mass. The IM-induced expressions of Muscle RING finger 1 (MuRF1) and atrogin-1, two muscle-specific E3 ubiquitin ligases, were decreased by administration of GYY4137 or NaHS. Both GYY4137 and NaHS treatments alleviated the IM-induced muscle fibrosis, as evidenced by decreases in collagen deposition and levels of tissue fibrosis biomarkers. Moreover, administration of GYY4137 or NaHS alleviated the IM-induced infiltration of CD45 leukocytes, meanwhile inhibited the expressions of the pro-inflammatory biomarkers in skeletal muscles. It was found that administration of either GYY4137 or NaHS significantly attenuated immobilization-induced oxidative stress as indicated by decreased HO levels and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivity, as well as increased total antioxidant capacity (T-AOC), nuclear factor erythroid-2-related factor 2 (NRF2) and NRF2 downstream anti-oxidant targets levels in skeletal muscles. Collectively, the present study demonstrated that treatment with either slow or rapid HS releasing donors protected mice against immobilization-induced muscle fibrosis and atrophy. The beneficial effects of HS on immobilization-induced skeletal muscle atrophy might be due to both the anti-inflammatory and anti-oxidant properties of HS.
慢性炎症和氧化应激是固定化诱导的肌肉萎缩发病机制中蛋白质合成与降解失衡的主要触发因素。本研究旨在阐明硫化氢（HS）这种具有强大抗炎和抗氧化特性的气体递质对固定化诱导的肌肉萎缩的影响。将小鼠分为对照组和固定化（IM）组，分别用缓慢释放HS的供体（GYY4137）或快速释放HS的供体（NaHS）处理14天。结果表明，GYY4137和NaHS处理均减少了IM诱导的肌肉损失，并增加了肌肉质量。给予GYY4137或NaHS可降低IM诱导的肌肉特异性E3泛素连接酶肌肉环指蛋白1（MuRF1）和atrogin-1的表达。GYY4137和NaHS处理均减轻了IM诱导的肌肉纤维化，胶原沉积减少和组织纤维化生物标志物水平降低证明了这一点。此外，给予GYY4137或NaHS减轻了IM诱导的CD45白细胞浸润，同时抑制了骨骼肌中促炎生物标志物的表达。研究发现，给予GYY4137或NaHS均可显著减轻固定化诱导的氧化应激，表现为HO水平降低、8-羟基-2'-脱氧鸟苷（8-OHdG）免疫反应性降低，以及骨骼肌中总抗氧化能力（T-AOC）、核因子红细胞2相关因子2（NRF2）和NRF2下游抗氧化靶点水平升高。总的来说，本研究表明，用缓慢或快速释放HS的供体处理可保护小鼠免受固定化诱导的肌肉纤维化和萎缩。HS对固定化诱导的骨骼肌萎缩的有益作用可能归因于HS的抗炎和抗氧化特性。
