Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Instituto de Bioquímica Médica Leopoldo de Meis (IBqM-LDM), Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
J Physiol. 2018 Jul;596(14):2901-2916. doi: 10.1113/JP275888. Epub 2018 Jun 19.
Cigarette smoke components directly alter muscle fatigue resistance and intracellular muscle fibre Ca handling independent of a change in lung structure. Changes in muscle vascular structure are associated with a depletion of satellite cells. Sarcoplasmic reticulum Ca uptake is substantially impaired in myofibres during fatiguing contractions in mice treated with cigarette smoke extract.
Cigarette smokers exhibit exercise intolerance before a decline in respiratory function. In the present study, the direct effects of cigarette smoke on limb muscle function were tested by comparing cigarette smoke delivered to mice by weekly injections of cigarette smoke extract (CSE), or nose-only exposure (CS) 5 days each week, for 8 weeks. Cigarette smoke delivered by either route did not alter pulmonary airspace size. Muscle fatigue measured in situ was 50% lower in the CSE and CS groups than in control. This was accompanied by 34% and 22% decreases in soleus capillary-to-fibre ratio of the CSE and CS groups, respectively, and a trend for fewer skeletal muscle actin-positive arterioles (P = 0.07). In addition, fewer quiescent satellite cells (Nes+Pax7+) were associated with soleus fibres in mice with skeletal myofibre VEGF gene deletion (decreased 47%) and CS exposed (decreased 73%) than with control fibres. Contractile properties of isolated extensor digitorum longus and soleus muscles were impaired. In flexor digitorum brevis myofibres isolated from CSE mice, fatigue resistance was diminished by 43% compared to control and CS myofibres, and this was accompanied by a pronounced slowing in relaxation, an increase in intracellular Ca accumulation, and a slowing in sarcoplasmic reticulum Ca uptake. These data suggest that cigarette smoke components may impair hindlimb muscle vascular structure, fatigue resistance and myofibre calcium handling, and these changes ultimately affect contractile efficiency of locomotor muscles independent of a change in lung function.
香烟烟雾成分直接改变肌肉疲劳抵抗力和细胞内肌肉纤维钙处理，而不改变肺结构。肌肉血管结构的变化与卫星细胞耗竭有关。在接受香烟烟雾提取物处理的小鼠进行疲劳收缩时，肌纤维中的肌浆网钙摄取量显著受损。
吸烟的人在呼吸功能下降之前就表现出运动不耐受。在本研究中，通过比较每周接受香烟烟雾提取物（CSE）注射或每周 5 天鼻腔暴露（CS）的小鼠，测试香烟烟雾对肢体肌肉功能的直接影响，共 8 周。两种途径输送的香烟烟雾均未改变肺气道大小。CSE 和 CS 组的肌肉疲劳原位测量值比对照组低 50%。这伴随着 CSE 和 CS 组比目鱼肌毛细血管与纤维比分别下降 34%和 22%，以及骨骼肌肌动蛋白阳性小动脉数量减少的趋势（P=0.07）。此外，与对照组纤维相比，具有骨骼肌血管内皮生长因子基因缺失（减少 47%）和 CS 暴露（减少 73%）的比目鱼肌中的静止卫星细胞（Nes+Pax7+）更少。从 CSE 小鼠分离的伸趾长肌和比目鱼肌的收缩性能受损。在 CSE 小鼠分离的屈趾短肌肌纤维中，与对照组和 CS 肌纤维相比，疲劳抵抗力降低了 43%，这伴随着明显的松弛减慢、细胞内 Ca 积累增加以及肌浆网 Ca 摄取减慢。这些数据表明，香烟烟雾成分可能会损害后肢肌肉血管结构、疲劳抵抗力和肌纤维钙处理，这些变化最终会影响运动肌肉的收缩效率，而与肺功能的变化无关。
