Tempol对高原缺氧致小鼠脑组织损伤的保护作用

Protective effects of Tempol against hypobaric hypoxia induced brain damage in mice

目的:研究Tempol对高原缺氧小鼠脑组织的保护作用及其机制。方法:将60只小鼠随机分为正常对照组、缺氧模型组、乙酰唑胺组和Tempol组,单次腹腔注射给药后,在模拟海拔8 000 m环境停留12 h,检测脑组织中H_2O_2、MDA、ATP酶和抗氧化酶的活性变化,蛋白印迹法检测HIF-1α、VEGF、Nrf2和HO-1蛋白的表达情况。结果:与正常对照组相比,缺氧模型组中H_2O_2和MDA含量显著增加,ATP酶和抗氧化酶活性显著减低,HIF-1α、VEGF、Nrf2和HO-1x蛋白表达增强。经Tempol预处理后能够显著降低高原缺氧小鼠脑组织中H_2O_2和MDA含量,提高抗氧化酶和ATP酶活性,降低HIF-1α和VEGF蛋白表达,显著提高Nrf2和HO-1蛋白的表达。结论:Tempol能够减轻高原缺氧脑组织损伤,作用机制可能与其能清除自由基,激活Nrf2/HO-1信号途径,提高抗氧化酶活性,降低机体氧化应激,改善能量代谢有关。

OBJECTIVE To evaluate the protective effect and mechanism of Tempol against hypobaric hypoxia induced brain damage in mice.METHODS Sixty BALB/C mice were randomly divided into normal control group,hypoxia model group,acetazolamide group and Tempol group.After single intraperitoneal injection,mice were exposed to hypobaric hypoxia（8000 m）for 12 h.The H2O2,MDA level,ATPase and antioxidant enzyme activity in brain were monitored.The expression levels of HIF-1α,VEGF,Nrf2 and HO-1 were determined by Western blotting.RESULTS The contents of H2O2 and MDA in hypoxia model group significantly increased while ATPase and antioxidant enzyme activity markedly decreased compared with the normal control group.Hypobaric hypoxia exposure significantly upregulated the expression levels of HIF-1α,VEGF,Nrf2 and HO-1.Prior administration of Tempol decreased the H2O2 and MDA levels and increased ATPase and antioxidant enzyme activity.Tempol inhibited the expressions of HIF-1αand VEGF,while further up regulated Nrf2 and HO-1 expressions.CONCLUSION The protection of Tempol against the hypobaric hypoxia induced brain injury can be explained in part by its free radical scavenging activity,improvement of antioxidant enzyme activity,the activation of the Nrf2/HO-1 pathway,alleviation of oxidative stress as well as amelioration of energy metabolism.