Basic and clinical studies asociated with hepatic reticulo endothelial system after major surgery

建立了用于严重感染（脓毒症）或肝功能衰竭基础研究的稳定失血性休克复苏实验动物模型。研究各脏器功能障碍的发生过程，客观评价肝网内皮功能。在该模型中，我们获得了与多器官衰竭密切相关的全身性炎症反应综合征，即最终器官损伤和脓毒症终末期的证据，表明该休克模型可用于模拟脓毒症和器官衰竭。尤其是肝功能衰竭。我们也证明了器官损伤。特别是肝功能衰竭，与微循环功能不全和炎症细胞（如中性粒细胞）的积累有关。因此，我们认为，阻断这些因素可能是治疗器官损伤的重要关键。肝网状内皮功能在概念上是宿主对大肠杆菌等细菌感染的主要防御系统，我们在一定程度上阐明了这种免疫反应在肝脏中的确切机制。此外，我们阐明了一氧化氮（NO）。它是一种强大的血管扩张剂，调节有机微循环，保护器官免受损害，参与杀死肝脏中的细菌。而。140被认为具有细胞损伤的作用。因此，调控选择性NO合成酶有望预防大手术后肝功能障碍。

A stable hemorrhagic shock-resuscitation model of experimental animals for the basic study of severe infection (sepsis) or hepatic failure was established. The process of each organ dysfunction were studied and the hepatic reticuloendothelial function was objectively evaluated using our model. In this model, the evidence of systemic inflammatory response syndrome which is closely associated with multiple organ failure known as ultimate organ injury and terminal stage of sepsis were obtained, indicating that this shock model is useful to simulate sepsis and organ failure. especially hepatic failure. We also demonstrated that the organ injury. Especially hepatic failure, were associated with microcirculatory insufficiency and the accumulation of inflammatory cells (e.g. neutrophils). We, therefore, concluded that the blockage against these factors was likely to the important key for the treatment of the organ injury. The hepatic reticuloendothelial function is conceptually major host defense system to the bacterial infection such as E.coli infection and we partly elucidated the precise mechanisms of this immune response in the liver. Additionally, we elucidated that nitric oxide (NO). which is strong vaso-dilator regulating the organic microcirculation to protect from organ damages, is to be involved in bacterial killing in the liver. Whereas. 140 are recognized to have the effect of cellular injury. Therefore, regulation of selective NO synthetase would be expected to prevent hepatic dysfunction after major operation.