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)，这是重症监护病房的主要死亡原因。革兰氏阴性细菌败血症的症状可以通过用内毒素治疗动物来实验复制，内毒素是革兰氏阴性细菌细胞壁的一种成分。脂多糖负责启动一系列高度复杂的级联事件，导致多器官损伤。活性氧物种也被认为作为末端效应分子发挥了重要作用。我们研究了HO-1诱导在腹腔注射脂多糖所致败血症MODS模型大鼠肠道组织损伤中的作用。结果发现，在十二指肠、空肠等上肠粘膜上皮细胞中，HO-1被显著诱导表达，而在回肠、结肠等下肠粘膜上皮细胞中，HO-1几乎不表达且不被诱导。相反，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，可增加黏膜上皮细胞的损伤和炎症，但对下肠无影响，提示HO-1的诱导及其活性的维持在保护肠道上皮细胞免受内毒素或脓毒症引起的氧化损伤中起关键作用。

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.