Kirova Iu I, Germanova É L, Luk'ianova L D
Fiziol Zh (1994). 2013;59(6):98-110.
Hypoxic preconditioning induces two-phase increase of HIF-1alpha expression in the neocortex of low-resistance rats. The first, brief phase appears after each hypoxic episode and rapidly disappears in normoxic conditions. The second increase in of HIF-1alpha expression occurs in 24 hours after the hypoxic episode. The phase-nature of HIF-1alpha expression corresponds to the dynamics of urgent and long-term resistance in low-resistance rats, which suggests the HIF-1alpha involvement in mechanisms of urgent and long-term adaptation. It was found that in the mode of preconditioning, hypoxic treatments mobilized the anti-oxidant system (activated Cu, Zn-SOD) and had no effect on the intensity of lipid peroxidation processes in neocortex (INH, 10% O2) or even decreased the content of lipid peroxidation products and oxidized glutathione in neocortical cells in the early post-hypoxic period (HBH-5000, 10.5% O2). Thus, ROS do not play a key role in the induction of HIF-1alpha expression and fast-response/long-term adaptation to O2 deficiency in hypoxia-sensitive animals. In high-resistance rats, hypoxia preconditioning does not influence the HIF-1alpha protein expression and the adaptation. Severe hypoxic modes (HBH-7000, 8% O2) caused activation of lipid peroxidation processes in neocortex of hypoxia-sensitive rats. With the pro-oxidant systems dominating over the anti-oxidant ones, the neocortical expression of HIF-1alpha was found to decrease, which was accompanied by the impairment of the mechanisms of fast-response/long-term adaptation to hypoxia.
低抗性大鼠新皮质中,低氧预处理诱导缺氧诱导因子-1α(HIF-1α)表达出现两阶段增加。第一阶段为短暂增加,每次低氧发作后出现,在常氧条件下迅速消失。第二阶段HIF-1α表达增加发生在低氧发作后24小时。HIF-1α表达的阶段性特征与低抗性大鼠的急性和长期抗性动态相对应,这表明HIF-1α参与了急性和长期适应机制。研究发现,在预处理模式下,低氧处理激活了抗氧化系统(激活铜、锌超氧化物歧化酶),对新皮质(INH,10%氧气)脂质过氧化过程的强度没有影响,甚至在低氧后早期(HBH-5000,10.5%氧气)降低了新皮质细胞中脂质过氧化产物和氧化型谷胱甘肽的含量。因此,活性氧在缺氧敏感动物中HIF-1α表达的诱导以及对缺氧的快速反应/长期适应中不起关键作用。在高抗性大鼠中,低氧预处理不影响HIF-1α蛋白表达和适应性。严重低氧模式(HBH-7000,8%氧气)导致缺氧敏感大鼠新皮质脂质过氧化过程激活。由于促氧化系统占主导地位超过抗氧化系统,发现新皮质中HIF-1α表达降低,同时伴有对缺氧的快速反应/长期适应机制受损。