Decline in the expression of copper/zinc superoxide dismutase in the kidney of rats with endotoxic shock: Effects of the superoxide anion radical scavenger, tempol, on organ injury
Decline in the expression of copper/zinc superoxide dismutase in the kidney of rats with endotoxic shock: Effects of the superoxide anion radical scavenger, tempol, on organ injury
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DOI：
10.1038/sj.bjp.0702123
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发表时间：
1998-10-01
影响因子：
7.3
通讯作者：
Thiemermann, C
中科院分区：
文献类型：
--
作者：
Leach, M;Frank, S;Thiemermann, C
1内毒素血症导致活性氧（ROS）的形成增加，这有助于脓毒性休克中的多器官功能障碍综合征（MODS）。本研究观察了内毒素对大鼠肾脏超氧化物歧化酶（SOD）两种亚型Cu/Zn-SOD（胞质）和Mn-SOD（线粒体）表达的影响，以及自由基清除剂tempol对脂多糖（LPS，E. 6 mg kg（-1）i.v.）2内毒素血症导致肾脏Cu/Zn-SOD mRNA和蛋白表达的快速但短暂的下降以及Mn-SOD mRNA表达的增加。内毒素血症6小时还引起低血压、急性肾功能不全、肝细胞损伤、胰腺损伤和血浆亚硝酸盐/硝酸盐水平的增加。3用tempol（100 mg kg（-1）静脉推注，在LPS之前15分钟，随后静脉输注30 mg kg（-1），n = 9）对循环衰竭无明显影响，但能减轻LPS引起的肾功能损害和肝细胞损伤/功能障碍。Tempol没有影响内毒素引起的亚硝酸盐/硝酸盐的升高。4这些结果表明，ROS（包括超氧阴离子）的形成增加，以及对此类ROS的防御不足，导致内毒素休克中肾脏和肝脏的损伤和功能障碍。
1 Endotoxaemia causes an enhanced formation of reactive oxygen species (ROS) which contribute to the multiple organ dysfunction syndrome (MODS) in septic shock. Here we investigate (i) the effects of endotoxin on the expression of two isoforms of superoxide dismutase (SOD), namely Cu/Zn-SOD (cytosol) and Mn-SOD (mitochondria) in the rat kidney, and (ii) the effects of the radical scavenger tempol on the MODS caused by lipopolysaccharide (LPS, E. coli, 6 mg kg(-1) i.v.) in the rat.2 Endotoxaemia resulted in a rapid, but transient, decline in the expression of both mRNA and protein of Cu/Zn-SOD as well as an increase in the expression of the mRNA of Mn-SOD in the kidney. Endotoxaemia for 6 h also caused hypotension, acute renal dysfunction, hepatocellular injury, pancreatic injury and an increase in the plasma levels of nitrite/nitrate.3 Pretreatment of rats with tempol (100 mg kg(-1) i.v. bolus injection, 15 min prior to LPS followed by an infusion of 30 mg kg(-1) i.v., n = 9) did not affect the circulatory failure, but attenuated the renal dysfunction and the hepatocellular injury/dysfunction caused by LPS. Tempol did not affect the rise in nitrite/nitrate caused by endotoxin.4 These results imply that an enhanced formation of ROS (including superoxide anions) in conjunction with inadequate defences against such ROS contributes to the injury and dysfunction of the kidney and the liver in endotoxic shock.