The multiple organs insult and compensation mechanism in mice exposed to hypobaric hypoxia

Ning Li,Hailing Yang,Yi Zhang,Jinrong Bai,Fangfang Fan,Tingting Kuang,Wenxiang Wang,Ke Chen,Qiuyue Li,Gang Fan,Xianli Meng

doi:10.1007/s12192-020-01117-w

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.

Highlights

Hypobaric hypoxia (HH) is the cardinal feature of the high-altitude environment
The increase of HIF-1α expression is related to hypoxic adaptation and the protection in the early stage of acute mountain sickness (AMS), but the prolongation of its downstream effector factor, vascular endothelial growth factor (VEGF), can induce excessive endothelial barrier dysfunction, increase vascular permeability, and eventually lead to high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE)
Hematoxylin & eosin (H&E) staining of brain tissue revealed the neurocyte Statistical analysis was conducted by independent sample T test shrinkage and chromatin dissolution in the cortex; the HH induces decreased activity of superoxide dismutase (SOD) in serum and tissue

Summary

Introduction

While the atmosphere is 21% oxygen at all altitudes, Previous evidences revealed that high altitude has stress detrimental influences on the functions of several cells due to free-radical damage sojourners, and mountaineers frequently experience different degrees of organ damage during highmountain journeys. HIF-1α is one of the most crucial signaling molecules which mediates the responses of mammalian cells to hypoxia by inducing the expression of adaptive gene products, such as EPO and VEGF. The increase of HIF-1α expression is related to hypoxic adaptation and the protection in the early stage of acute mountain sickness (AMS), but the prolongation of its downstream effector factor, VEGF, can induce excessive endothelial barrier dysfunction, increase vascular permeability, and eventually lead to high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). Oxidative stress refers to the imbalance between the production of reactive oxygen species and the ability of endogenous antioxidant system to remove these reactive oxygen species

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