Diaphragmatic fatigue during sepsis-Mechanisms and therapy

本研究旨在探讨腹腔脓毒症大鼠离体血管收缩力的变化及其机制。腹腔内脓毒症是使用盲肠结扎穿孔技术（CLP）。通过离体血管收缩特性和力-频率曲线评价血管收缩力。在第一项研究中，我们调查了CLP后血管收缩力的时程变化。CLP后10小时开始出现膈肌收缩功能障碍，CLP后16小时进一步减少。在第二项研究中，我们研究了PEG-SOD、PEG-CAT和DMSO对脓毒性腹膜炎大鼠离体血管收缩力和MDA水平以及两种主要抗氧化酶超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）活性的影响。CLP前30 min和CLP后12 h分别腹腔注射PEG-SOD、PEG-CAT和DMSO。CLP后膈肌MDA水平显著升高。PEG=SOD、PEG-CAT和DMSO可明显改善CLP后大鼠血管的收缩功能，并可抑制CLP后血管MDA水平的升高。CLP后膈肌SOD活性明显升高。这些结果表明，几种类型的氧源性自由基在CLP后血管收缩性降低中起作用。

We investigated the alteration and mechanisms in diaphragmatic contractility in intra-abdominal sepsis in vitro. Intra-abdominal sepsis was produced using the cecal ligation and perforation technique (CLP). We assessed the diaphragmatic contractility by twitch characteristics and force-frequency curves in vitro. In the first study, we investigated the time course changes in diaphragmatic contractility after CLP. Diaphragmatic contractile dysfunction was began to develop 10hr after CLP and further reduction was observed 16hr after CLP. In the second study, we investigated the effects of PEG-SOD, PEG-CAT and DMSO on diaphragmatic contractility and MDA levels in septic peritonitis and the activities of two main antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) in vitro. PEG-SOD, PEG-CAT and DMSO were administered intraperitoneally 30 min before and 12h after CLP. Diaphragmatic MDA levels were significantly elevated after CLP. PEG=SOD, PEG-CAT and DMSO significantly improved diaphragmatic contractility and prevented the elevation in diaphragmatic MDA levels after CLP. Diaphragmatic SOD activities were significantly increased after CLP. These results suggest that several types of oxygen-derived free radicals play a role in the reduction in diaphragmatic contractility after CLP.