Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Partizan Zheleznyak st., 1., Krasnoyarsk, Russian Federation, 660022.
Altai Medical Institute of Postgraduate Education, Polzunova st., 34a, Barnaul, Russian Federation, 656000.
Neuromolecular Med. 2022 Jun;24(2):155-168. doi: 10.1007/s12017-021-08672-0. Epub 2021 Jun 11.
The mechanisms and signaling pathways of the neuroprotective effects of hypercapnia and its combination with hypoxia are not studied sufficiently. The study aims to test the hypothesis of the potentiating effect of hypercapnia on the systems of adaptation to hypoxia, directly associated with A1-adenosine receptors and mitochondrial ATP-dependent K+ -channels (mitoK-channels). We evaluated the relative number of A1-adenosine receptors and mitoK-channels in astrocytes obtained from male Wistar rats exposed to various respiratory conditions (15 times of hypoxia and/or hypercapnia). In addition, the relative number of these molecules in astrocytes was evaluated on an in vitro model of chemical hypoxia, as well as in the cerebral cortex after photothrombotic damage. This study indicates an increase in the relative number of A1-adenosine receptors in astrocytes and in cells next to the stroke region of the cerebral cortex in rats exposed to hypoxia and hypercapnic hypoxia, but not hypercapnia alone. Hypercapnia and hypoxia increase the relative number of mitoK-channels in astrocytes and in cells of the peri-infarct region of the cerebral cortex in rats. In an in vitro study, hypercapnia mitigates the effects of acute chemical hypoxia observed in astrocytes for A1-adenosine receptors and mitoK-channels. Hypercapnia, unlike hypoxia, does not affect the relative number of A1 receptors to adenosine. At the same time, both hypercapnia and hypoxia increase the relative number of mitoK-channels, which can potentiate their protective effects with combined exposure.
高碳酸血症及其与缺氧结合的神经保护作用的机制和信号通路尚未得到充分研究。本研究旨在检验高碳酸血症增强与 A1-腺苷受体和线粒体 ATP 依赖性 K+通道（mitoK 通道）直接相关的缺氧适应系统的假设。我们评估了暴露于各种呼吸条件（15 次缺氧和/或高碳酸血症）的雄性 Wistar 大鼠星形胶质细胞中 A1-腺苷受体和 mitoK 通道的相对数量。此外，还评估了这些分子在星形胶质细胞化学缺氧体外模型以及光血栓损伤后的大脑皮质中的相对数量。这项研究表明，在暴露于缺氧和高碳酸缺氧的大鼠中，星形胶质细胞和大脑皮质中风区附近的细胞中 A1-腺苷受体的相对数量增加，但单独的高碳酸血症则没有。高碳酸血症和缺氧增加了星形胶质细胞和大脑皮质梗死周边区细胞中线粒体 K+通道的相对数量。在体外研究中，高碳酸血症减轻了星形胶质细胞中观察到的急性化学缺氧对 A1-腺苷受体和 mitoK 通道的影响。与缺氧不同，高碳酸血症不会影响星形胶质细胞中 A1 受体与腺苷的相对数量。同时，高碳酸血症和缺氧都会增加 mitoK 通道的相对数量，这可以增强它们在联合暴露时的保护作用。
