Expression Of Hif-1α In Kidney Tissue Of Rats Exposured To An Altitude Of 4600m

Background The Hypoxia Inducible Factor-1 (HIF-1) was discovered during the studies related to the gene expression of Erythropoietin (EPO) induced by hypoxia. HIF-1 is not only the nuclear adjustment factor of gene transcription, but also a peculiar mediator between hypoxia adaption and pathological reaction. Being a protein factor combined by heterodimers and Deoxyribo Nucleic Acid (DNA), HIF-1 consists of two subunits, namely, HIF-1αand HIF-1β. These two subunits both contain bHIF- Per/ARNT/Sim (bHIF-PAS) structure domain. HIF-1αonly exists in nucleus of hypoxia cell , but HIF-1βis essentially insensitive to O2 availability and exists in both nucleus and cytoplasm. HIF-1αis expressed highest in kidney, heart and thymus of mouse, followed by liver, spleen, lung and testis, while the skeletal muscle expressed lowest. Under normal condition, the HIF-1αis expressed by each tissue at a low level, but the dependence of HIF-1αto time and hypoxia degree rose under the hypoxia condition . Since HIF-1αinfluences the production of erythrocyte and vascellum, the hyperplasia and apoptosis of cell and other physiological, pathological procedures, and stimulates tissues to adaptively respond to hypoxia, the HIF-1αis therefore a cell factor to protect the kidney. There exist reports related to such issue both at home and abroad, but mainly focused on acute or chronic kidney injury, ischemia and/or hypoxia induced kidney injury, glycuresis-related kidney disease and transplant, etc, which reflected the scare researches with regard to high altitude hypoxia.Method In order to discuss expreesion of HIF-1 on high altitude hypoxia, we transported 50 male Wistar rats from Lanzhou(1500m) to Ke-ke-xi-li Natural Reservation areas(4600m) in Qinghai province by truck.Tish testing group were anesthetiezd and all time sample were gaind at different time point including 1d,3d,7d,14d and 21d,respectively,we used the automatic biochemistry analyzer to examine the kidney funtion of rats,and immunohistochemiscal streptavidin-perosidase(SP) staining were used to evaluate the levels of HIF-1α.Maenwhile the control group was set up in Lanzhou(1500m).Results The rats renal functions were increased initialy and then decreased after entered the plateau area.There was significant difference between the control group and testing groups.The level of HIF-1αin rats increased initialy after exposure altitude(0.37±0.12),and reached its peak of 3d(3.68±0.20).Then it decreased gradually and was similar to the control group at 21d.The immunohistochemical staining demonstrated that HIF-1αdiatributed mainly in proximal,distal and collecting tubular epithelial cells in medulla more than in cortex.There was less expression in glomrulus.Conclusions This study observed the function of kidney and variations of HIF-1αin kidney tissue under high altitude hypoxia condition. Several conclusions can be drawn from this study. Firstly, the rising trend of HIF-1αwas observed during the initial stage of hypoxia, this high expression of HIF-1αmight be induced by stress reaction to hypoxia,and could reduce the impact to kidney tissues induced by hypoxia. Secondly, along with the adaption and negative feedback of related factors, HIF-1αwas expressed at a relatively lower level. To sum up, the variation reveals that the expression of HIF-1αof rats can be induced by high altitude hypoxia and the kidney was guarded through this procedure. Our results provided the theoretical foundation for the prevention and treatment of kidney injury induced by high altitude hypoxia.