Molecular Mechanism Of Hypoxic Tolerance Induced By Hyperbaric Oxygen

Hypoxia is a state of oxygen deficiency in the body which is sufficient to cause an impairment of function. It is caused by the reduction in partial pressure of oxygen, inadequate oxygen transport, or the inability of the tissues to use oxygen. Hypoxia may induce dysfunction of systems. It is the major pathophysiological feature of various diseases such as chronic obstructive pulmaonary disease, cyanotic congenital heart defects and tumor progression. It also naturally occurs in acute athletics and in populations living at high altitude.Hypoxia preconditioning was the classical method of hypoxia adaptation. It has been known for many years that both humans and animals could adapt to hypoxia by hypoxia preconditioning, while the mechanism of hypoxia preconditioning increases tolerance to hypoxia-induced dysfunction is still unclear and there are some obvious limitations of the management.The mechanism of hypoxia preconditioning correlates with the induction of the hypoxia-inducible factor (HIF), a transcription factor heterodimeric complex composed of inducible HIF-la and constitutive HIF-16 proteins. HIF-1 is a master regulator of oxygen homeostasis that controls angiogenesis, erythropoiesis, and glycolysis via transcriptional activation of target genes under hypoxic conditions. These target genes, including vascular endothelial growth factor, erythropoietin, glucose transporters, glycolytic enzymes, and many other genes, are also induced following hypoxia-induced tolerance. Some or all of these genes may contribute to hypoxia preconditioning. HIF-la accumulates under hypoxic conditions, whereas HIF-1β is constitutively expressed. HIF-la is not regulated only by the oxygen tension, but also by various other atimuli, such as transition metals, nitric oxide, reactive oxygen species, cytokine, and mechanical stresses.Apparently, there are obvious differences between the effects on organism of hyperbaric oxygen (HBO) and hypoxia. HBO can improve the content of internal oxygen and carbon dioxide; on the contrary, hypoxia can reduce the content of oxygen and carbon dioxide. In fact, there are a lot of similar effects on organism between them. For example, They can all suppress the energy metabolism, reduce ATP content in the brain, increaseinternal free radical and H+ content, damage the organism, even cause the individual death. HBO and hypoxia preconditioning can all enhance the anti-oxidant ability, prevent the chronic hyperbaric oxygen toxicity of animal, lighten the damage of central nervous system ischemia, and improve the sensitiveness to HBO of central nervous system. These phenomena indicate that HBO can improve the ability of resists the hypoxic damages, and HBO may be the substituting scheme of hypoxia preconditioning.Comprehensive the above results, we infer that hypoxic tolerance may be induced by HBO. HBO has been used in humans in the treatment of ischemic disease, stroke, CO poisoning, air embolism and decompression sickness. Elevation of the inspired partial pressure of oxygen causes oxidative stress to every organ. Some researches have proved that preconditioning with HBO and hypoxia can induce tolerance against spinal cord ischemia in rabbits and hyperbaric oxygenation can induce tolerance against permanent focal cerebral ischemia in mice. These results indicate hypoxic tolerance may be induced by HBO. Because there are many advantages of HBO preconditioning compared to hypoxia preconditioning. HBO preconditioning is safer and more efficient than hypoxia preconditioning. If HBO preconditioning can be carried into execution, it may provide a new means to induce hypoxic tolerance and to improve the hypoxic diseases.The objective of this work was to examine whether HBO exposure provide additive protection of the body against subsequent hypoxia, and the mechanism of HBO preconditioning. Therefore, we carry on the following study.1. To investigate the hypoxic tolerance and physical stamina in hypoxia, the effects of HBO on survival time during normobaric hypoxia exposure and performance of the forced swimming test (FST) under hypoxia were measured. To investigate the effects of HBO on brain edema and pulmonary edema after acute hypoxia, water content was determined using wet and dry weights method. To evaluate the effects of HBO on the changes of blood-brain barrier (BBB) and blood-air barrier permeability after acute hypoxia, Evans blue was used. To investigate the effect of HBO on the physical stamina, the time to exhaustive swimming and the blood lactate (BLA), the activity of superoxide dismulase (SOD) and methylenedioxyamphetamine (MDA) after swimming for 90 min were measured.2. To study the mechanisms of hypoxic tolerance induced by HBO exposure, the expression of HIF-1a and EPO was determined in cerebral cortex and hippocampus during HBO by immunohistochemistry and Western blot analysis.3. Investigate the expression of HIF-la and its mRNA in HepG2 cell during HBO by...