Cigarette Smoking Exacerbates Skeletal Muscle Injury without Compromising Its Regenerative Capacity
Cigarette Smoking Exacerbates Skeletal Muscle Injury without Compromising Its Regenerative Capacity
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DOI：
10.1165/rcmb.2019-0106oc
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发表时间：
2020-02-01
影响因子：
6.4
通讯作者：
Vlahos, Ross
中科院分区：
文献类型：
--
作者：
Chan, Stanley M. H.;Cerni, Claudia;Vlahos, Ross
慢性阻塞性肺疾病患者的骨骼肌功能障碍对生活质量和生存率产生负面影响。吸烟（CS）是慢性阻塞性肺疾病和骨骼肌功能障碍的主要危险因素;然而，CS如何影响骨骼肌功能仍然是个谜。为了检查CS对骨骼肌炎症和再生的影响，雄性BALB/c小鼠在通过氯化钡注射诱导肌肉损伤之前暴露于CS 8周，并在损伤后维持CS方案长达21天。氯化钡注射导致胫骨前肌的结构损伤，导致收缩功能下降，CS暴露使其恶化。CS暴露引起肌肉萎缩（总重量和肌纤维横截面积减少）和改变纤维类型组成（氧化纤维减少31%）。随着时间的推移，CS暴露引起的收缩功能和肌纤维横截面积损失逐渐恢复。卫星细胞是肌肉干细胞，赋予骨骼肌适应不断变化的需求的可塑性。CS暴露钝化卫星细胞内的Pax 7+集中核，从而防止这些肌肉干细胞的激活。最后，CS引发肌肉炎症;特别是F4/80 +单核细胞向损伤部位的募集加剧，伴随沿着增强的促炎细胞因子表达。总之，CS暴露放大了骨骼肌损伤部位的局部炎症反应，这与受损的卫星细胞活化有关，导致恶化的肌肉损伤和收缩功能，而对恢复结果没有可检测的影响。
Skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease negatively impacts quality of life and survival. Cigarette smoking (CS) is the major risk factor for chronic obstructive pulmonary disease and skeletal muscle dysfunction; however, how CS affects skeletal muscle function remains enigmatic. To examine the impact of CS on skeletal muscle inflammation and regeneration, male BALB/c mice were exposed to CS for 8 weeks before muscle injury was induced by barium chloride injection, and were maintained on the CS protocol for up to 21 days after injury. Barium chloride injection resulted in architectural damage to the tibialis anterior muscle, resulting in a decrease contractile function, which was worsened by CS exposure. CS exposure caused muscle atrophy (reduction in gross weight and myofiber cross-sectional area) and altered fiber type composition (31% reduction of oxidative fibers). Both contractile function and loss in myofiber cross-sectional area by CS exposure gradually recovered over time. Satellite cells are muscle stem cells that confer skeletal muscle the plasticity to adapt to changing demands. CS exposure blunted Pax7 + centralized nuclei within satellite cells and thus prevented the activation of these muscle stem cells. Finally, CS triggered muscle inflammation; in particular, there was an exacerbated recruitment of F4/80 + monocytic cells to the site of injury along with enhanced proinflammatory cytokine expression In conclusion, CS exposure amplified the local inflammatory response at the site of skeletal muscle injury, and this was associated with impaired satellite cell activation, leading to a worsened muscle injury and contractile function without detectable impacts on the recovery outcomes.