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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 study the protective effect of Tempol on brain tissue in hypoxia mice and its mechanism. Methods: Sixty mice were randomly divided into normal control group, hypoxia model group, acetazolamide group and Tempol group. After a single intraperitoneal injection, the mice were maintained at a simulated altitude of 8 000 m for 12 h. The activities of H 2 O 2, MDA, ATPase and antioxidant enzyme were detected by Western blotting. The expressions of HIF-1α, VEGF, Nrf2 and HO-1 protein were detected by Western blotting. Results: Compared with the normal control group, the content of H 2 O 2 and MDA in the hypoxia model group increased significantly, the activity of ATPase and antioxidant enzyme decreased significantly, and the expression of HIF-1α, VEGF, Nrf2 and HO-1x protein increased. After Tempol pretreatment, H 2 O 2 and MDA contents, antioxidative enzymes and ATPase activities, HIF-1α and VEGF protein expression and Nrf 2 and HO-1 protein expression in brain tissue of hypoxic mice significantly decreased. CONCLUSION: Tempol can reduce brain injury caused by hypoxia in plateau. Its mechanism may be related to its ability to scavenge free radicals, activate Nrf2 / HO-1 signaling pathway, increase antioxidant enzyme activity, reduce oxidative stress and improve energy metabolism.