The multiple organs insult and compensation mechanism in mice exposed to hypobaric hypoxia
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ORIGINAL PAPER
The multiple organs insult and compensation mechanism in mice exposed to hypobaric hypoxia Ning Li 1,2 & Qiuyue Li 1,2 & Jinrong Bai 3 & Ke Chen 3 & Hailing Yang 1,2 & Wenxiang Wang 3 & Fangfang Fan 1,2 & Yi Zhang 1,2 & Xianli Meng 1,4 & Tingting Kuang 1 & Gang Fan 1 Received: 9 November 2019 / Revised: 23 April 2020 / Accepted: 1 May 2020 # The Author(s) 2020
Abstract This study was first and systematically conducted to evaluate the hypoxia response of the brain, heart, lung, liver, and kidney of mice exposed to an animal hypobaric chamber. First, we examined the pathological damage of the above tissues by Hematoxylin & eosin (H&E) staining. Secondly, biochemical assays were used to detect oxidative stress indicators such as superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), and oxidized glutathione (GSSG). Finally, the hypoxia compensation mechanism of tissues was evaluated by expression levels of hypoxia-inducible factor 1 alpha (HIF-1α), erythropoietin (EPO), and vascular endothelial growth factor (VEGF). During the experiment, the mice lost weight gradually on the first 3 days, and then, the weight loss tended to remain stable, and feed consumption showed the inverse trend. H&E staining results showed that there were sparse and atrophic neurons and dissolved chromatin in the hypoxia group. And hyperemia occurred in the myocardium, lung, liver, and kidney. Meanwhile, hypoxia stimulated the enlargement of myocardial space, the infiltration of inflammatory cells in lung tissue, the swelling of epithelial cells in hepatic lobules and renal tubules, and the separation of basal cells. Moreover, hypoxia markedly inhibited the activity of SOD and GSH and exacerbated the levels of MDA and GSSG in the serum and five organs. In addition, hypoxia induced the expression of HIF-1α, EPO, and VEGF in five organs. These results suggest hypoxia leads to oxidative damage and compensation mechanism of the brain, heart, lung, liver, and kidney in varying degrees of mice. Keywords Hypoxia . Oxidative stress . HIF-1α . EPO . VEGF . Compensation mechanism
Introduction Hypobaric hypoxia (HH) is the cardinal feature of the high-altitude environment. While the atmosphere is 21% oxygen at all altitudes,
* Tingting Kuang [email protected] * Gang Fan [email protected] 1
School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2
Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
3
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
4
Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
barometric pressure falls upon ascent, and with it the partial pressure of oxygen (PO2) (Murray 2016), and the deleterious effects of high altitude are primarily caused by the low inspired PO2 (West 2012). At 1500 m, PO2 is about 84% of the value at s
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