Shindoh C, Hida W, Ohkawara Y, Yamauchi K, Ohno I, Takishima T, Shirato K
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 1):1690-6. doi: 10.1164/ajrccm.152.5.7582314.
We studied gene expression and production of TNF-alpha in the diaphragm tissue and changes of muscle contractile properties after endotoxin injection (Escherichia coli, 20 mg/kg) in 88 rats. We assessed the muscle contractile properties by force-frequency curves and twitch kinetics using dissected diaphragm muscle strips. The peak tensions of force-frequency curves decreased from control values (2.15 +/- 0.2 kg/cm2) up to 4 h (0.81 +/- 0.17, p < 0.001), and then increased at 6 h (1.36 +/- 0.19, p < 0.05) after endotoxin injection. The cytotoxic activity on L929 cells in arterial blood samples maximally increased at 2 h (p < 0.001), then decreased to 6 h (p < 0.05). TNF-alpha mRNA in diaphragm tissue was detected by Northern blot method at 1 and 1.5 h, and the immunolocalization of TNF-alpha was evaluated at 2 and 4 h by immunohistochemistry in the muscle tissues. Furthermore, preinjection with anti-m TNF-alpha antibody prevented the decrement of force-frequency curves after endotoxin injection of 10 microliters/kg. From this evidence that TNF-alpha gene expression and production occurred in the diaphragm tissue, but anti-m TNF-alpha antibody preinjection prevented the deterioration of diaphragm muscle contractile properties, we suggest that TNF-alpha may act on muscle cells extracellularly.
我们研究了88只大鼠在内毒素（大肠杆菌，20mg/kg）注射后膈肌组织中肿瘤坏死因子-α（TNF-α）的基因表达、产生情况以及肌肉收缩特性的变化。我们使用分离的膈肌肌条，通过力-频率曲线和单收缩动力学来评估肌肉收缩特性。内毒素注射后，力-频率曲线的峰值张力从对照值（2.15±0.2kg/cm²）在4小时内下降（0.81±0.17，p<0.001），然后在6小时时升高（1.36±0.19，p<0.05）。动脉血样本中对L929细胞的细胞毒性活性在2小时时最大程度升高（p<0.001），然后在6小时时下降（p<0.05）。通过Northern印迹法在1小时和1.5小时检测膈肌组织中的TNF-α mRNA，并在2小时和4小时通过免疫组织化学评估肌肉组织中TNF-α的免疫定位。此外，预先注射抗小鼠TNF-α抗体可防止在注射10微升/千克内毒素后力-频率曲线的下降。基于TNF-α基因表达和产生发生在膈肌组织中，但预先注射抗小鼠TNF-α抗体可防止膈肌肌肉收缩特性恶化这一证据，我们认为TNF-α可能在细胞外作用于肌肉细胞。
