The role of glial activation on the pathogenesis of septic encephalopathy

脓毒症通常导致多器官功能障碍综合征（MODS），这是重症监护病房死亡的主要原因。革兰氏阴性细菌脓毒症的症状可以通过实验再现用脂多糖治疗动物，脂多糖是革兰氏阴性细菌细胞壁的一种成分。LPS负责启动一系列高度复杂的级联事件，导致多器官损伤。活性氧也被认为作为末端执行器分子发挥重要作用。我们研究了HO-1在腹腔注射LPS致脓毒性MODS大鼠模型中肠组织损伤中的作用。我们发现，在LPS处理后，HO-1在十二指肠和空肠等上肠粘膜上皮细胞中被显著诱导，而在回肠和结肠等下肠中，HO-1几乎没有表达，也没有被诱导。相比之下，肠组织损伤酸性炎症在下肠比在上肠更明显。用HO-1抑制剂预处理动物可增强上肠粘膜上皮细胞损伤和炎症，但对下肠没有作用，这表明HO-1的诱导和维持其适当活性似乎对保护肠上皮细胞免受LPS或败血症诱导的氧化损伤至关重要。

Sepsis often leads to a multiple organ dysfunction syndrome (MODS), a leading cause of death in intensive care units. Symptoms of gram-negative bacterial sepsis can be reproduced experimentally by treatment of animals with LPS, a component of the cell wall of Gram-negative bacteria. LPS is responsible for initiating a series of highly complex cascading events leading to multiple organ damage. Reactive oxygen species are also thought to play an important role as an end-effector molecule. We examined the role of HO-1 induction in the intestinal tissue injury in a rat model of septic MODS produced by intraperitoneal injection of LPS. We found that HO-1 was markedly induced following LPS treatment in the mucosal epithelial cells in the Upper intestine such as the duodenum and the jejunum, whereas HO-1 was hardly expressed and not induced by the same treatment in the lower intestine such as the ileum and the colon. In contrast, the intestinal tissue injury acid inflammation was more pronounced in the lower intestine than in the upper intestine. Pretreatment of animals with HO-1 inhibitor augmented mucosal epithelial cell injuries and inflammation in the upper intestine, but not in the lower intestine, suggesting that HO-1 induction and the maintenance of its appropriate activity appear to be critical in the protection of the intestinal epithelial cells from an oxidative injury induced by LPS, or sepsis.