血红素加氧酶-2 基因敲除对Fe^(2+)诱导的小鼠脑氧化应激损伤中基底节细胞的保护作用(英文)

Heme oxygenase-2 gene deletion protects basal ganglia cells from oxidative injury induced by free Fe^(2+)

目的:观察血红素加氧酶2 基因敲除对Fe2+诱导的脑氧化应激损伤的保护作用。方法:采用立体定向法注射10μl FeCl2(10 mmol/L)至血红素加氧酶2 基因敲除小鼠及野生型小鼠右侧纹状体,制备Fe2+诱导的脑氧化应激损伤模型。测量损伤24 h后损伤区域脑水肿程度。利用MTT法测量损伤72 h后细胞生存率。利用蛋白印迹法检测损伤72 h后细胞脑组织氧化反应性蛋白及脂质氧化蛋白含量。结果:血红素加氧酶2 基因敲除小鼠脑水肿程度显著低于野生型小鼠;损伤区域细胞生存率显著高于野生型小鼠;血红素加氧酶2 基因敲除小鼠损伤区域组织氧化反应性蛋白及脂质氧化蛋白含量显著低于野生型小鼠。结论:血红素加氧酶2参与了Fe2+诱导的脑氧化应激损伤,基因敲除血红素加氧酶2 对脑氧化应激损伤具有保护作用。

Objective:To determine whether heme oxygenase-2(HO-2) gene deletion can attenuate oxidative injury induced by free Fe 2+. Methods:Stereotactic injection of 10 μl sterile FeCl 2 (10 mmol/L) was made into the right striata of HO-2 knockout mice and wild-type mice. Brain edema severity was measured at 24 h. Cell viability, protein oxidation, and lipid oxidation of the basal ganglia were determined at 72 h. Western blot analysis was applied for heme oxygenase-1 (HO-1) measurement. Results: Brain water content significantly decreased in HO-2 knockout mice at 24 h compared with wild-type mice. Protein oxidation and lipid oxidation significantly decreased in HO-2 knockout mice at 72 h compared with wild-type mice, while the striatal cell viability increased significantly. HO-1 expression at baseline and 72 h was also similar to that in wild-type mice.Conclusion:These results show that HO-2 gene deletion can protect basal ganalia cells from free Fe 2+-mediated oxidative stress injury,suggesting that selective inhibition of HO-2 may have a protective effect on brain oxidative injury.