Mechanism of multiple organ failure caused by interaction of nitric oxide and oxidant stress

研究1：一氧化氮(NO)与自由基的相互作用可能是脑缺血再灌注损伤中多器官衰竭的原因。本研究采用大鼠部分肝缺血再灌流模型，观察一氧化氮对氧化应激的影响，探讨缺血再灌注时细胞损伤的机制。建立大鼠肝外侧叶缺血再灌流模型。连续给予N-硝基-L-精氨酸甲酯(L-NAME)、L-精氨酸(L-Arg)或生理盐水后，测定各组I/R叶和非I/R叶组织血流量及氧化和还原谷胱甘肽浓度。抑制NO的产生恶化了I/R叶和非I/R叶的组织血流量、肝损伤和氧化应激。应用L-精氨酸后，I/R叶组织血流量仅一过性增加，肝损伤加重，氧化应激加重。研究二：脓毒症常导致多器官功能衰竭。为了揭示脓毒症器官衰竭的机制，我们应用药物释放系统(DDS)建立了一种新的可复制的脓毒症动物模型。植入含有内毒素的DDS的大鼠在72小时内保持高水平的内毒素，并表现出脓毒症状态。

Research 1 : Interaction of nitric oxide (NO) and free radical is suspected the cause of multiple organ failure in ischemia reperfusion injury. In this research, we evaluated effect of nitric oxide on oxidant stress to estimate mechanism of cellular injury in ischemia reperfusion using partial hepatic ischemia-reperfusion model. Rats were subjected to ischemia and reperfusion in the lateral lobe of the liver. After continuous administration of NG-nitro-L-arginine methyl ester (L-NAME), L-arginine (L-Arg) or saline, we evaluated tissue blood flow and concentrations of oxidized and reduced glutathione in the I/R-lobe and the non-I/R-lobe in each group. Inhibition of NO production deteriorated tissue blood flow, hepatic injury and oxidant stress in both the I/R-lobe and the non-I/R-lobe. Administration of L-Arg had only transient increase of tissue blood flow in the I/R-lobe, moreover deteriorated hepatic injury and oxidant stress.Research 2 : Sepsis often causes multiple organ failure. To reveal the mechanism of septic organ failure, we developed a novel reproducible septic animal model applying drug delivery system (DDS). Rats implanted with DDS contained with lipopolysaccharide maintained high blood levels of endotoxin for 72 hours, and also exhibited septic condition.