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被怀疑是缺血再灌注损伤中多器官功能衰竭的原因。本研究采用部分肝缺血-再灌注模型，评价一氧化氮对氧化应激的影响，探讨缺血-再灌注中细胞损伤的机制。大鼠肝外侧叶缺血再灌注。在连续给药ng -硝基-l -精氨酸甲酯（L-NAME）、l -精氨酸（L-Arg）或生理盐水后，我们评估各组组织血流量和I/ r叶和非I/ r叶中氧化和还原性谷胱甘肽的浓度。抑制NO的产生可恶化I/ r叶和非I/ r叶的组织血流、肝损伤和氧化应激。l -精氨酸仅能短暂增加I/ r叶组织血流量，并加重肝损伤和氧化应激。研究2：败血症常引起多器官衰竭。为了揭示脓毒性器官衰竭的机制，我们建立了一种新的可重复的脓毒性动物模型，应用药物传递系统（DDS）。注射含脂多糖DDS的大鼠在72小时内维持高血内毒素水平，并出现脓毒症。

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.