High Altitude Adaptation Genes Regulate The Hemoglobin By HIF-2α

Objective:1. Establishing a Wistar rats model of acute exposed to high altitude.2. Measuring the rat blood indicators and pathology of major organs in acute hypoxia and early adaption process.3. Study on the expression differences of HIF-2α(EPAS1) and related adaption genes in mRNA and protein level, during the process of exposure to different altitude plateau and initial acclimation.4. Exploring the biological significance of gene and protein expression differences and the mechanism of the hemoglobin regulation.Methods:1. The rats were randomly divided into plain group, one day after acute hypoxia, three days and five days exposed to high altitude. Detecting the blood gas by abdominal aorta and blood routine by venous blood.2. HE staining for three altitude plateau rats’ tissues of heart, liver, brain, lung and kidney biopsy, compared changes of microscopic morphological.3. RT-PCR assays to detect different altitudes and different altitude exposure time for the differentiation of EPAS1, EGLN1, PPARA, EPO and VEGF gene expression in rats’blood and tissues.4. Enzyme-linked Immunity assays to detect different altitudes and different altitude exposure time for the differences of endothelial PAS protein, PHD protein, peroxisome proliferator-activated receptor a, erythropoietin and vascular endothelial growth factors expression in rats’blood and tissues.Results:1. Compared with the plain group, the red blood cell count, hemoglobin concentration, hematocrit and mean corpuscular hemoglobin concentration were observed significant differences in three-day groups and five-day groups. Except RBC, other indicators within three days were significantly increased, but decreased to normal levels after five days, or slightly above the normal level. The partial pressure of oxygen, carbon dioxide and oxygen saturation were decreased significantly within1day, but gradually increased after3days.2. Organizations including heart, liver, brain, lung, kidney had different degrees of hypoxia injuries in two altitudes, the results suggested that the most serious damage happened in4300m altitude. The main manifestations were inflammatory infiltration, epidermal hyperplasia, nuclear condensation, etc.3. During the processes of hypoxia acclimation, the downstream genes of HIF-2α including EPO, VEGF, PPARA were up-regulated, however, the upstream gene EGLN1was inhibited. The protein expression had different tendency in different tissues, and the most obvious effects were in liver and kidney.Conclusion:1. HIF-2α played an important roles in regulations of acute hypoxia and acclimation, and regulated the related genes.2. HIF-2α possible changed the RBC by regulate the EPO, in order to increase the hemoglobin concentration. The most obvious effects were in liver and kidney.