Supinski G, Nethery D, DiMarco A
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Am Rev Respir Dis. 1993 Nov;148(5):1318-24. doi: 10.1164/ajrccm/148.5.1318.
Recent studies have suggested that free radicals contribute to the diaphragmatic dysfunction observed in sepsis. However, previous work has not determined which species of free radicals are responsible for producing these effects or whether the intercostal muscles are affected similarly during sepsis. The purpose of this study was to examine these issues using a hamster model of endotoxin-mediated sepsis in which diaphragm and intercostal muscle function was assessed on muscle strips excised from these animals after killing. Several groups of animals were studied, including animals injected with (1) saline, (2) endotoxin, (3) endotoxin plus active PEG-SOD, a superoxide scavenger, (4) endotoxin plus active PEG-catalase, a hydrogen peroxide scavenger, (5) endotoxin plus DMSO, a hydroxyl scavenger, and (6) endotoxin plus denatured PEG-SOD. We found that endotoxin administration elicited significant reductions in diaphragm and intercostal muscle contractility. In each of the three groups of animals to which active free radical scavengers were administered, the effects of endotoxin were attenuated. Denatured PEG-SOD did not protect the respiratory muscles from endotoxin-mediated dysfunction, however. These data indicate that both the diaphragm and intercostal muscles are affected similarly by sepsis; moreover, several free radical species (superoxide ions, hydrogen peroxide, and hydroxyl ions) play a role in mediating this type of injury.
最近的研究表明，自由基会导致脓毒症中观察到的膈肌功能障碍。然而，先前的研究尚未确定哪种自由基会产生这些影响，也未确定脓毒症期间肋间肌是否受到类似影响。本研究的目的是使用内毒素介导的脓毒症仓鼠模型来研究这些问题，在处死动物后，从这些动物身上切下肌肉条，评估膈肌和肋间肌的功能。研究了几组动物，包括注射了(1)生理盐水、(2)内毒素、(3)内毒素加活性聚乙二醇超氧化物歧化酶（一种超氧化物清除剂）、(4)内毒素加活性聚乙二醇过氧化氢酶（一种过氧化氢清除剂）、(5)内毒素加二甲基亚砜（一种羟基清除剂）以及(6)内毒素加变性聚乙二醇超氧化物歧化酶的动物。我们发现，给予内毒素会导致膈肌和肋间肌收缩力显著降低。在给予活性自由基清除剂的三组动物中，内毒素的影响均减弱。然而，变性聚乙二醇超氧化物歧化酶并不能保护呼吸肌免受内毒素介导的功能障碍影响。这些数据表明，脓毒症对膈肌和肋间肌的影响相似；此外，几种自由基（超氧离子、过氧化氢和羟基离子）在介导这类损伤中起作用。
