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[缺氧适应不同阶段大鼠新皮质细胞缺氧诱导因子表达的表型特征及氧化还原状态]

[Phenotypic characteristics of factor expression induced by hypoxia and redox status of the rat neocortical cells at different stages of adaptation to hypoxia].

作者信息

Kirova Iu I, Germanova É L, Luk'ianova L D

出版信息

Fiziol Zh (1994). 2013;59(6):98-110.

Abstract

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.

摘要

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。

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