The Research Of HIF-2? And STfR Expression Level In Rat Model With Chronic Mountain Sickness

Background: CMS is a serious public health problem to plateau people. For a long time, scholars extensively studied CMS but it is still unclear. Recently scholars have found that HIF for the regulation of iron metabolism plays an important role in the pathogenesis of the CMS. In hypoxia condition, HIF-2 may regulate the expression of TfR via combining with the HRE that located in the transcription start site of the TfR mRNA. There's also a view that the regulator of iron metabolism is HIF-1. The scholars have showed that hypoxia changed the iron metabolism significantly, but the way how HIF regulate iron metabolism in CMS has not been fully elucidated. Objective: This experiment detected the level of HIF-2? mRNA, HIF-2? protein, sTfR and SF in Rat Model with Chronic Mountain Sickness to research the possible mechanism of the CMS disease. Which to further explore the function of HIF-2? in CMS disease, and the relation between HIF-2? and iron metabolism. Methods: 50 healthy male SD rats from Xi'an to Xining were involved in this study. After one weeks of adaptive feeding, the experiment was performed. 50 rats were randomized into six groups, which is hypoxia seven days group, hypoxia fifteen days group and CMS group, normoxia seven days group, normoxia fifteen days group, normoxia thirty days group. After seven, fifteen and thirty days, the rats were anesthetized respectively and we tested: ?Blood routine test, SF was measured by nephelometry; ?The rat liver HIF-2? mRNA levels were measured using qRT-PCR; ?The protein level of HIF-2? was detected respectively by IHC; ?The protein level of sTfR was detected respectively by ELISA; ?All dates in the figures were treated with statistical software SPSS19.0. Calculations for statistical divergence among two groups were carried out by Independent samples Student's t-test. Calculations for statistical divergence among multiple groups were carried out by variance analysis. All factors were analyzed by coefficient of productmoment correlation. ?=0.05 was considered as significant level. Results: ? The level of HIF-2? mRNA: There are significantly statistical differences between hypoxia thirty days group and hypoxia seven days group(P<0.01). The level of HIF-2? mRNA in CMS group is significantly higher than it in normoxia thirty days group(P<0.05). ?The level of HIF-2? protein: Compare hypoxia seven days group with hypoxia fifteen days group and CMS group, the level of HIF-2? protein expression in hypoxia seven days group is significantly lower than that in the other two groups(P<0.05). The level of HIF-2? protein in CMS group is significantly higher than it in normoxia thirty days group(P<0.05). ?The level of sTfR: There are significantly statistical differences between hypoxia thirty days group and hypoxia seven days group about the level of sTfR protein(P<0.05). The level of sTfR protein in hypoxia three groups are significantly increased than their own normoxia control groups(P<0.05). ?The HIF-2? protein expression level have no correlation with the sTfR protein expression level. Conclusions: Under hypoxia condition, the levels of HIF-2? and sTfR expression are significantly increased. With the increase of hypoxia time, the levels of HIF-2? and sTfR expression gradually increase, and maintain high expression in the CMS group. The reason for this result may be associated with the excessive proliferation of RBC and the raising iron requirement. There's no correlation between HIF-2? protein and sTfR protein.