Department of Preventive Medicine, Wenzhou Medical College, Wenzhou, Zhejiang 325035, PR China.
Biochem Biophys Res Commun. 2011 Jan 7;404(1):559-63. doi: 10.1016/j.bbrc.2010.12.025. Epub 2010 Dec 8.
Knockout of copper, zinc-superoxide dismutase (SOD1) and (or) cellular glutathione peroxidase (GPX1) has been reported to have dual impacts on coping with free radical-induced oxidative injury. Because bacterial endotoxin lipopolysaccharide (LPS) triggers inflammatory responses involving the release of cytokines, nitric oxide and superoxide in targeted organs such as liver, in this study we used SOD1 knockout (SOD1-/-), GPX1 knockout (GPX1-/-), GPX1 and SOD1 double-knockout (DKO) and their wild-type (WT) mice to investigate the role of these two antioxidant enzymes in LPS-induced oxidative injury in liver. Mice of the four genotypes (2 month old) were killed at 0, 3, 6 or 12 h after an i.p. injection of saline or 5 mg LPS/kg body weight. The LPS injection caused similar increase in plasma alanine aminotransferase among the four genotypes. Hepatic total glutathione (GSH) was decreased (P<0.05) compared with the initial values by the LPS injection at all time points in the WT mice, but only at 6 and 12 h in the other three genotypes. The GSH level in the DKO mice was higher (P<0.05) than in the WT at 6 h. Although the LPS injection resulted in substantial increases in plasma NO in a time-dependent manner in all genotypes, the NO level in the DKO mice was lower (P<0.05) at 3, 6 and 12 h than in the WT. The level in the GPX1-/- and SOD1-/- mice was also lower (P<0.05) than in the WT at 3 h. The LPS-mediated hepatic protein nitration was detected in the WT and GPX1-/- mice at 3, 6 or 12 h, but not in the SOD1-/-. In conclusion, knockout of SOD1 and (or) GPX1 did not potentiate the LPS-induced liver injury, but delayed the induced hepatic GSH depletion and plasma NO production.
铜锌超氧化物歧化酶（SOD1）和（或）细胞谷胱甘肽过氧化物酶（GPX1）的敲除已被报道对自由基诱导的氧化损伤有双重影响。由于细菌内毒素脂多糖（LPS）引发涉及细胞因子、一氧化氮和超氧阴离子释放的靶向器官（如肝脏）炎症反应，在这项研究中，我们使用 SOD1 敲除（SOD1-/-）、GPX1 敲除（GPX1-/-）、GPX1 和 SOD1 双重敲除（DKO）及其野生型（WT）小鼠来研究这两种抗氧化酶在 LPS 诱导的肝脏氧化损伤中的作用。四种基因型（2 月龄）的小鼠在腹腔注射生理盐水或 5mg LPS/kg 体重后 0、3、6 或 12 小时处死。LPS 注射使四种基因型的血浆丙氨酸氨基转移酶均有类似增加。与 WT 小鼠的初始值相比，LPS 注射后所有时间点肝总谷胱甘肽（GSH）均降低（P<0.05），但在其他三种基因型中仅在 6 和 12 小时时降低。与 WT 相比，DKO 小鼠在 6 小时时 GSH 水平更高（P<0.05）。尽管 LPS 注射在所有基因型中均导致血浆 NO 水平呈时间依赖性显著增加，但 DKO 小鼠的 NO 水平在 3、6 和 12 小时时均低于 WT（P<0.05）。GPX1-/-和 SOD1-/-小鼠的水平也低于 WT（P<0.05）在 3 小时时。在 WT 和 GPX1-/-小鼠中，LPS 介导的肝蛋白硝化在 3、6 或 12 小时时检测到，但在 SOD1-/-中未检测到。总之，SOD1 和（或）GPX1 的敲除并未增强 LPS 诱导的肝损伤，但延迟了诱导的肝 GSH 耗竭和血浆 NO 产生。
