Pathophyisological analysis of endotoxemia and septisemia & effectiveness of suppression of liver macrophages.

我们的目标是建立内毒素血症和败血症引起的肝功能衰竭的治疗方法。因此，对肝巨噬细胞的活化机制进行了分析。在这项研究中，我们澄清了氯化钆（GdC13）降低了注射致死剂量内毒素的大鼠的死亡率。然而，血浆肿瘤坏死因子（TNR）水平不受GdC13治疗的影响。单核吞噬细胞系统主要位于肝脏和脾脏。我们怀疑脾巨噬细胞可能补偿肝巨噬细胞的功能障碍，血浆TNF水平受到脾巨噬细胞的影响。我们研究了脾巨噬细胞在血浆TNF变化方面的功能，并通过免疫组织化学研究了脾切除或不切除肝巨噬细胞功能障碍情况下巨噬细胞的再生情况。我们得到的结果是，注射GdC13后，大的肝脏巨噬细胞被清除，脾脏巨噬细胞不受GdC13治疗的影响。TNF水平也不受脾巨噬细胞的影响，也不能补偿GdC13治疗后肝巨噬细胞的功能障碍。在今后对内毒素血症和败血症的研究中，应着重分析肝巨噬细胞的活化机制。

Our goal of this project is establishment of therpy for hepatic failure caused by endotoxemia and septisemia. So analysis of mechanisms of activation of liver macrophage have been done.In this study, we clarified that gadolinium chloride (GdC13) reduced mortality in rats injected with a lethal dose of endotoxin. However, plasma tumor necrosis factor (TNR) levels were not affected by GdC13 treatment. The mononuclear phagocyte system is situateed mainly in the liver and spleen. We suspected that the spleen macrophages probably compensate for dysfunction of liver macrophages and plasma TNF levels are affected by splenic macrophages. We investigated the function of splenic macrophages with respect to changes in plasma TNF,and carried out immunohistochemical study to investigate the repopulation of macrophges under the condition of dysfunction of liver macrophages with or without splenectomy. We got the results that large liver macrophages were eliminated after GdC13 injection and the splenic marcophages were not affected by GdC13 treatment. TNF levels were also not affected by the splenic macrophages and they do not compensate for dysfunction of liver macrophages after GdC13 treatment. In our future research about endotoxemia and septisemia, we should focus on an anlysis of mechanisms of activation of liver macrophages.