Kirova Yu I
Patol Fiziol Eksp Ter. 2014 Oct-Dec(4):40-7.
The study compared effects of different hypobaric hypoxia regimens (14% O2, 10.5% O2, and 8% O2; 1 hour; 15 days) on parameters of the glutathione system, intensity of free radical oxidation, and intensity of lipid peroxidation in cerebral cortex (CC) of rats with different, genetically predetermined resistance to acute hypoxia. In normoxia, baseline concentrations of oxidized glutathione (0.155 ± 0.011 nmol/mg protein) and hydroperoxide metabolites (50.4 ± 2.62 cumene hydroperoxide equivalents/g tissue) were 20% lower in CC of low-resistance (LR) rats than in high-resistance (HR) rats (0.191 ± 0.013 nmol/mg protein; 63.0 ± 3.46 cumene hydroperoxide equivalents/g tissue, respectively). Baseline activities of the glutathione cycle enzymes, glutathione peroxidase (31.2 ± 1.59 nmol/min/mg protein) and glutathione reductase (28.5 ± 1.49 nmol/min/mg protein), were 30% lower in LR rat CC than in HR rat CC (47.0 ± 2.41; 433 ± 2.26 nmol/min/mg protein, respectively). These data suggested more efficient antioxidant defense of CC tissue in LR rats than in HR rats. The phenotypic difference in CC tissue redox properties between two rat phenotypes remained in hypoxia. The efficiency of glutathione system in regulation of CC redox homeostasis was shown to depend on both severity and duration of hypoxic exposures and on individual tolerability of hypoxia, i.e., this efficiency was genetically predetermined. The glutathione system maintains its regulatory properties in a broader range of lowered pO2 values and during longer hypoxic exposures. in LR rat CC than in HR rat CC. For this reason, activation of free radical processes and development of oxidative stress induced by single or repeated hypoxic exposures are prevented or alleviated in LR rat CC but not in HR rat CC. The obtained data strongly justify the need for selection of hypoxic exposure regimens for therapeutic hypoxic preconditioning. Apparently the hypoxic exposures not associated with signs of oxidative stress should be considered optimum.
该研究比较了不同低压低氧方案（14%氧气、10.5%氧气和8%氧气；1小时；15天）对具有不同遗传预先确定的急性低氧抗性的大鼠大脑皮层（CC）中谷胱甘肽系统参数、自由基氧化强度和脂质过氧化强度的影响。在常氧条件下，低抗性（LR）大鼠CC中氧化型谷胱甘肽（0.155±0.011 nmol/mg蛋白质）和氢过氧化物代谢产物（50.4±2.62枯烯氢过氧化物当量/g组织）的基线浓度比高抗性（HR）大鼠低20%（分别为0.191±0.013 nmol/mg蛋白质；63.0±3.46枯烯氢过氧化物当量/g组织）。谷胱甘肽循环酶谷胱甘肽过氧化物酶（31.2±1.59 nmol/min/mg蛋白质）和谷胱甘肽还原酶（28.5±1.49 nmol/min/mg蛋白质）的基线活性在LR大鼠CC中比在HR大鼠CC中低30%（分别为47.0±2.41；433±2.26 nmol/min/mg蛋白质）。这些数据表明，LR大鼠CC组织的抗氧化防御比HR大鼠更有效。两种大鼠表型之间CC组织氧化还原特性的表型差异在低氧条件下仍然存在。结果表明，谷胱甘肽系统调节CC氧化还原稳态的效率取决于低氧暴露的严重程度和持续时间以及个体对低氧的耐受性，即这种效率是由基因预先确定的。谷胱甘肽系统在更广泛的降低的pO2值范围内和更长时间的低氧暴露期间保持其调节特性。在LR大鼠CC中比在HR大鼠CC中更有效。因此，单次或重复低氧暴露诱导的自由基过程的激活和氧化应激的发展在LR大鼠CC中得到预防或减轻，但在HR大鼠CC中则不然。获得的数据有力地证明了为治疗性低氧预处理选择低氧暴露方案的必要性。显然，与氧化应激迹象无关的低氧暴露应被视为最佳方案。
