The Expression Of HIF-2α Protein In Tissues Of Rats Model With Chronic Mountain Sickness

Objective To establish CMS rats model using the hypobaric oxygen chamber. The HIF-2α expressions in the heart, liver, spleen, kidney tissues were detected by immunohistochemistry method(IHC) and the HIF-2α concentration in serum was determined by ELISA. In addition, the correlation between HIF-2α and HGB in CMS rats was analysed to explore the role of HIF-2α in the red blood cells accumulation of CMS.Methods 49 SPF level male Wistar rats were transported from Lanzhou to Xining. After two weeks, they were randomly divided into the CMS model group(24 rats) and the control group(25 rats). The rats which raised in hypobaric oxygen chamber(simulated altitude of 5000 meters, high pressure 395 mm Hg to 410 mm Hg, oxygen pressure 11.3 k Pa to 11.4 k Pa, temperature of 26 degrees ~ 28 degrees, humidity ranged from 38% to 56%) as the CMS model group, and the rats which raised in Xining under natural conditions(altitude of 2260 meters, temperature of 20 degrees to 25 degrees, humidity is 40% ~ 60%) as the control group. After 30 days,(1) the arterial blood was collected for blood routine test;(2) The serum was separated for HIF-2α protein detection by ELISA;(3) The tissues of heart, liver, spleen and kidney were taken for HIF-2α protein detection by immunohistochemistry(IHC);(4) 5 rats of CMS model group and 6 rats of control group were randomly selected for pulmonary artery pressure detection.Results(1) The mean HGB was higher in the CMS model group(223±16 g/L) than that in the control group(183±8 g/L)(P<0.05). The mean HCT was also higher in CMS model group(66.0±4.4%) than that in the control group(50.5±1.9%)(P<0.05). But the mean PLT was lower in CMS model group [(586±140)×109/L] than that in the control group [(988±112)×109/L](P<0.05);(2) IHC results showed that there was no significant difference in the expression of HIF-2α in heart, liver and spleen tissues between these two groups(P>0.05). However, the expression of HIF-2α in kidney tissues was higher in the CMS model group than that in the control group(P<0.05).(3) ELISA results showed that the serum level of HIF-2α in CMS model group(8.2±2.6 ng/ml) was higher than that in the control group(4.6±2.7 ng/ml)(P<0.05). But there was no significant correlation between serum HIF-2α content and HGB(r=0.054, P=0.827).(4) The pulmonary artery pressure(m PAP) of CMS model group(66.06±17.36 mm Hg) was higher than that of the control group(29.78±4.47 mm Hg)(P<0.05).Conclusions According to the HGB, HCT and pulmonary artery pressure, it could be considered that CMS animal model was successfully made using hypobaric oxygen chamber in this study; The level of HIF-2α protein was higher in kidney and serum in CMS model rats, which may participate in the mechanism of excessive accumulation of red blood cells in CMS.