The Research Of Hepcidin And TWSG1 Expression Level In Rat Model With Chronic Mountain Sickness

Backgrounds and objective: CMS is a kind of clinical syndrome characterized by excessive erythrocytosis and serious hypoxemia, which is mainly caused by hypoxia. Over the years, scholars have preceded extensive studies of CMS, however the study of iron metabolism is rare. Hepcidin is very important in the regulation of iron level. Scholars further discovered TWSG1 play an important role in the maintenance of iron homeostasis, which can inhibit the BMP-Smad signal transduction indirect inhibition of hepcidin synthesis. Therefore, in this assay, we manufacture CMS rat model by simulating altitude of 5000 m to study the levels of TWSG1 and hepcidin comparing to normoxia group, thus to explore the regulation of TWSG1 to hepcidin in CMS rats.Methods: 50 male healthy rats bought in Xian were randomized into six groups: hypoxia seven day, hypoxia fifteen day, hypoxia thirty day(CMS), normoxia seven day, normoxia fifteen day, normoxia thirty day. After seven, fifteen and thirty days, we tested: Red blood cell count; The rat liver hepcidin and TWSG1 m RNA levels were measured by q RT-PCR; The protein level of TWSG1 was deteceted by IHC; All datas were treated with statistical software SPSS20.0. Calculations for statistical divergence among two groups were carried out by Independent samples Student’s t-test. Calculations for statistical diverge among multiple groups were carried out by variance analysis. All factors were analyzed by Spearman rank correlation. α=0.05 was considered as significant level.Results: ⑴The level of HAMP m RNA expression, hypoxia thirty day(CMS) was significantly lower than hypoxia seven day(P<0.05); hypoxia fifteen day and hypoxia thirty day(CMS) were significantly lower than their normoxia control groups(both P<0.05);⑵The level of TWSG1 m RNA expression, hypoxia fifteen day was significantly higher than hypoxia seven day(P<0.05), hypoxia thirty day(CMS) was significantly higher than hypoxia seven day and fifteen day(both P<0.05); hypoxia seven day was significantly lower than normoxia seven day(P<0.05), hypoxia fifteen day and hypoxia thirty day(CMS) were significantly higher than their normoxia control groups(both P<0.05).⑶The level of TWSG1 protein, hypoxia fifteen day was significantly higher than hypoxia seven day(P<0.01), hypoxia thirty day(CMS) was significantly higher than hypoxia seven day and fifteen day(both P<0.01); hypoxia fifteen day and hypoxia thirty day(CMS) were significantly higher than their normoxia control groups(both P<0.05).⑷The TWSG1 m RNA expression level had no correlation with the HAMP m RNA expression level in six groups(P>0.05).Conclusions: Decreased hepcidin expression has been reported in response to hypoxia condition, and maintained a low concentration in CMS. However TWSG1 expression was increased in response to hypoxia condition and gradually increased with the increase of hypoxia days, and it was highly expressed in CMS. TWSG1 level had no correlation with the hepcidin level.