Sakaguchi Shuhei, Furusawa Shinobu
First Department of Hygienic Chemistry, Tohoku Pharmaceutical University, Sendai, Japan.
FEMS Immunol Med Microbiol. 2006 Jul;47(2):167-77. doi: 10.1111/j.1574-695X.2006.00072.x.
This review describes the role of oxidative stress caused by endotoxin challenge in sepsis or septic shock symptoms. We observed that endotoxin injection resulted in lipid peroxide formation and membrane damage (near 60-150 kDa) in the livers of experimental animals, causing decreased levels of scavengers or quenchers of free radicals. The administration of alpha-tocopherol completely prevented injury to the liver plasma membrane caused by endotoxin, and suggested that lipid peroxidation by free radicals might occur in a tissue ischemic state, probably by disseminated intravascular coagulation (DIC), in endotoxemia. In mice, depression of Ca(2+)-ATPase activity in the liver plasma membrane may contribute to the membrane damage caused by endotoxin, and the increase of Ca(2+) in the liver cytoplasm may partially explain the oxidative stress that occurs in endotoxemia. It seems that endotoxin-induced free radical formation is regulated by Ca(2+) mobilization. Moreover, we have suggested that the oxidative stress caused by endotoxin may be due, at least in part, to the changes in endogenous zinc or selenium regulation during endotoxemia. Interestingly, the extent of TNF-alpha-induced oxidative stress may be the result of a synergism between TNF-alpha and gut-derived endotoxin. It is likely that bacterial or endotoxin translocation plays a significant role in TNF-alpha-induced septic shock. On the other hand, although nitric oxide (NO) has been implicated in the pathogenesis of vascular hyporesponsiveness and hypotension in septic shock in our experimental model, it is unlikely that NO plays a significant role in liver injury caused by free radical generation in endotoxemia.
本综述描述了内毒素激发引起的氧化应激在脓毒症或脓毒性休克症状中的作用。我们观察到，给实验动物注射内毒素会导致其肝脏中脂质过氧化物形成以及膜损伤（60 - 150 kDa附近），导致自由基清除剂或猝灭剂水平降低。给予α-生育酚可完全预防内毒素对肝细胞膜的损伤，这表明自由基引起的脂质过氧化可能发生在内毒素血症的组织缺血状态下，可能是通过弥散性血管内凝血（DIC）。在小鼠中，肝细胞膜中Ca(2 +)-ATP酶活性的降低可能导致内毒素引起的膜损伤，而肝细胞质中Ca(2 +)的增加可能部分解释了内毒素血症中发生的氧化应激。似乎内毒素诱导的自由基形成受Ca(2 +)动员调节。此外，我们提出内毒素引起的氧化应激可能至少部分归因于内毒素血症期间内源性锌或硒调节的变化。有趣的是，TNF-α诱导的氧化应激程度可能是TNF-α与肠道来源的内毒素之间协同作用的结果。细菌或内毒素移位可能在TNF-α诱导的脓毒性休克中起重要作用。另一方面，尽管在我们的实验模型中一氧化氮（NO）与脓毒性休克中血管反应性降低和低血压的发病机制有关，但NO在内毒素血症中自由基生成引起的肝损伤中不太可能起重要作用。
