Beijing Institute of Basic Medical Sciences, Beijing, China.
Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320231177189. doi: 10.1177/03946320231177189.
High-altitude cerebral edema (HACE) is considered to be the end-stage of acute mountain sickness (AMS); however, its pathophysiological mechanism remains unknown. Increasing evidences support that inflammation is an important risk factor for the occurrence of HACE. Including our published papers, previous studies demonstrated that the levels of IL-6, IL-1β, and TNF-α in both serum and hippocampus were increased in the mouse HACE model induced by LPS stimulation combined with hypobaric hypoxia exposure; however, the expression profile of other cytokines and chemokines remains unknown.
This study was to analyze the expression profile of cytokines and chemokines in the HACE model.
The mouse HACE model was established by LPS stimulation combined with hypobaric hypoxia exposure (LH). The mice were divided into the normoxic group, LH-6 h group, LH-1 d group, and LH-7 d group. Brain water content (BWC) was determined using the wet/dry weight ratio. The levels of 30 cytokines and chemokines in the serum and hippocampal tissue were detected using LiquiChip. The mRNA expression of cytokines and chemokines in hippocampal tissue were determined by -PCR.
In the current study, we found that the brain water content was increased after the combinational treatment of LPS and hypobaric hypoxia. The results of LiquiChip showed that, in the serum and hippocampal tissue, most factors in all 30 cytokines and chemokines were dramatically upregulated at 6 h, and then declined at the 1st d and 7th d. Among these factors, G-CSF, M-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β were all increased in both serum and hippocampal tissue at 6 h. In addition, the results of -PCR showed the mRNA levels of G-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β in hippocampal tissue were dramatically upregulated at 6 h.
This study showed that the dynamic expression profile of 30 cytokines and chemokines in a mouse HACE model induced by LPS plus hypobaric hypoxia. The levels of G-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β in both serum and hippocampus were significantly increased at 6 h, which may be involved in the occurrence and development of HACE.
高原脑水肿（HACE）被认为是急性高原病（AMS）的终末阶段；然而，其病理生理机制尚不清楚。越来越多的证据表明，炎症是 HACE 发生的一个重要危险因素。包括我们已发表的论文在内，以前的研究表明，LPS 刺激联合低压低氧暴露诱导的小鼠 HACE 模型中，血清和海马中的 IL-6、IL-1β 和 TNF-α 水平升高；然而，其他细胞因子和趋化因子的表达谱尚不清楚。
本研究旨在分析 HACE 模型中细胞因子和趋化因子的表达谱。
通过 LPS 刺激联合低压低氧暴露（LH）建立小鼠 HACE 模型。将小鼠分为常氧组、LH-6 h 组、LH-1 d 组和 LH-7 d 组。采用湿重/干重比测定脑水含量（BWC）。采用 LiquiChip 检测血清和海马组织中 30 种细胞因子和趋化因子的水平。采用实时定量 PCR 检测海马组织中细胞因子和趋化因子的 mRNA 表达。
在本研究中，我们发现 LPS 和低压低氧联合处理后脑水含量增加。LiquiChip 的结果表明，在血清和海马组织中，所有 30 种细胞因子和趋化因子中的大多数因子在 6 h 时均显著上调，然后在第 1 天和第 7 天下降。在这些因子中，G-CSF、M-CSF、MCP-1、KC、MIG、Eotaxin、Rantes、IP10、IL-6、MIP-2 和 MIP-1β 在 6 h 时均在血清和海马组织中升高。此外，实时定量 PCR 的结果表明，海马组织中 G-CSF、MCP-1、KC、MIG、Eotaxin、Rantes、IP10、IL-6、MIP-2 和 MIP-1β 的 mRNA 水平在 6 h 时显著上调。
本研究显示，LPS 加低压低氧诱导的小鼠 HACE 模型中 30 种细胞因子和趋化因子的动态表达谱。G-CSF、MCP-1、KC、MIG、Eotaxin、Rantes、IP10、IL-6、MIP-2 和 MIP-1β 在血清和海马中的水平在 6 h 时显著升高，这可能与 HACE 的发生发展有关。
