Tregub Pavel P, Malinovskaya Natalia A, Morgun Andrey V, Osipova Elena D, Kulikov Vladimir P, Kuzovkov Dmitry A, Kovzelev Pavel D
Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Partizan Zheleznyak st., 1., Krasnoyarsk, 660022, Russia; Altai Medical Institute of Postgraduate Education, Polzunova st., 34a, 656000, Barnaul, Russia.
Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Partizan Zheleznyak st., 1., Krasnoyarsk, 660022, Russia.
Respir Physiol Neurobiol. 2020 Jul;278:103442. doi: 10.1016/j.resp.2020.103442. Epub 2020 Apr 17.
The mechanisms and signalling pathways of the neuroprotective effect of hypercapnia and its combination with hypoxia are poorly understood. The study aims to test the hypothesis about the potentiating effect of hypercapnia on hypoxia adaptation systems directly related to hypoxia-induced factor 1α (HIF-1α). In this study we assessed HIF-1α content in hippocampal extracts and astrocytes obtained from Wistar male rats exposed to different respiratory conditions (7- or 15-fold of hypoxia and/or hypercapnia). In addition, HIF-1α content in astrocytes was assessed in in vitro model of chemical hypoxia as well as in the cerebral cortex after photothrombotic damage of this brain region. This study indicates increased levels of HIF1α in hippocampal extracts, astrocytes, and in cells of the near-stroke region of the cerebral cortex in rats exposed to hypoxia and hypercapnic hypoxia, but not hypercapnia alone. In in vitro study, hypercapnia facilitates the effects of acute chemical hypoxia observed in astrocytes. Thus, hypercapnia does not increase the level of transcription factor HIF-1α. However, the combined effects of hypercapnia and hypoxia in in vitro simulations of acute chemical hypoxia potentiate the accumulation of HIF-1α.
高碳酸血症及其与低氧联合作用的神经保护效应的机制和信号通路目前仍知之甚少。本研究旨在验证关于高碳酸血症对与低氧诱导因子1α（HIF-1α）直接相关的低氧适应系统具有增强作用的假说。在本研究中，我们评估了从暴露于不同呼吸条件（7倍或15倍低氧和/或高碳酸血症）的雄性Wistar大鼠获取的海马提取物和星形胶质细胞中的HIF-1α含量。此外，在化学性低氧的体外模型以及该脑区光血栓损伤后的大脑皮质中评估了星形胶质细胞中的HIF-1α含量。本研究表明，暴露于低氧和高碳酸血症低氧环境的大鼠，其海马提取物、星形胶质细胞以及大脑皮质近中风区域细胞中的HIF1α水平升高，但单独高碳酸血症环境下则不然。在体外研究中，高碳酸血症可促进星形胶质细胞中急性化学性低氧的效应。因此，高碳酸血症不会增加转录因子HIF-1α的水平。然而，在急性化学性低氧的体外模拟中，高碳酸血症和低氧的联合作用会增强HIF-1α的积累。
