Reid W D, Huang J, Bryson S, Walker D C, Belcastro A N
School of Rehabilitation Sciences, University of British Columbia Pulmonary Research Laboratory, Vancouver, Canada.
J Appl Physiol (1985). 1994 Jan;76(1):176-84. doi: 10.1152/jappl.1994.76.1.176.
The purpose of this study was to determine whether ventilatory failure is associated with muscle fiber damage and myofibrillar protein alterations. Ventilatory failure was induced by tightening a polyvinyl band around the trachea of hamsters (TB; n = 14) for 6 days, which resulted in severe respiratory acidosis (PCO2: 97.9 +/- 29.6 vs. 51.6 +/- 19.6 Torr; pH: 7.16 vs. 7.35), hypoxemia (PO2: 42.8 +/- 16.8 vs. 65.9 +/- 25.8 Torr), and increased pulmonary resistance (1.89 +/- 1.61 vs. 0.29 +/- 0.27 cmH2O.ml-1 x min; P < 0.05). The point-counting technique of hematoxylin- and eosin-stained cross sections showed a higher area fraction of abnormal muscle and inflammatory cells in the costal [0.133 +/- (SE) 0.33 vs. 0.040 +/- 0.010] and crural regions (0.069 +/- 0.020 vs. 0.012 +/- 0.003) of the diaphragm in TB hamsters than in control hamsters. Electron micrographs revealed sarcomeric disruption and Z band streaming in the diaphragm of TB hamsters. Myofibrillar changes of the diaphragm associated with ventilatory failure were quantitative (i.e., a lower yield of purified myofibrils) but not qualitative (similar sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles); however, sulfhydryl group reactivities were reduced (P < 0.05). Proteolysis of purified myofibrils from the diaphragm digested with calpain showed faster degradation rates for tropomyosin and alpha-actinin but not for all proteins for the TB animals. Ventilatory failure induced by resistive loading was associated with diaphragm injury; some of this injury was linked to changes in myofibrillar complexes, specifically their susceptibility to calpain-mediated degradation.
本研究的目的是确定通气衰竭是否与肌纤维损伤和肌原纤维蛋白改变有关。通过在仓鼠气管周围收紧聚乙烯带6天来诱导通气衰竭（TB组；n = 14），这导致了严重的呼吸性酸中毒（PCO2：97.9±29.6对比51.6±19.6 Torr；pH：7.16对比7.35）、低氧血症（PO2：42.8±16.8对比65.9±25.8 Torr）以及肺阻力增加（1.89±1.61对比0.29±0.27 cmH2O·ml-1×min；P < 0.05）。苏木精-伊红染色横断面的点计数技术显示，与对照仓鼠相比，TB组仓鼠膈肌的肋区[0.133±（标准误）0.33对比0.040±0.010]和腿区（0.069±0.020对比0.012±0.003）中异常肌肉和炎症细胞的面积分数更高。电子显微镜照片显示TB组仓鼠膈肌中肌节破坏和Z带流。与通气衰竭相关的膈肌肌原纤维变化是定量的（即纯化肌原纤维的产量较低）而非定性的（十二烷基硫酸钠-聚丙烯酰胺凝胶电泳蛋白质谱相似）；然而，巯基反应性降低（P < 0.05）。用钙蛋白酶消化的膈肌纯化肌原纤维的蛋白水解显示，TB组动物的原肌球蛋白和α-辅肌动蛋白的降解速度更快，但并非所有蛋白质都是如此。阻力负荷诱导的通气衰竭与膈肌损伤有关；这种损伤部分与肌原纤维复合物的变化有关，特别是它们对钙蛋白酶介导降解的敏感性。
