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| The Effect of Exposure to Chronic Intermittent Hypoxia on Hepatic Iron Metabolism in Rats |
| SONG Jixian, CHEN Qi, JIA Cuiling, et al |
| Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine / Hebei University of Traditional Chinese Medicine, Hebei Shijiazhuang 050200, China |
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Abstract Objective: To establish a rat model of chronic intermittent hypoxia (CIH) to explore the effect of CIH exposure on hepatic iron metabolism and the specific mechanism. Methods: The CIH rat model was established (the rats were placed in the animal intermittent hypoxia chamber,and the O2 concentration was reduced to 5% by 100% N2 in the first 1.5 min,and the O2 concentration was increased to 21% by 100% O2 in the last 1.5 min.Each cycle lasted for 3min,8h/d,35d).The normoxia control group rats were placed in the same chamber filled with normal air).HE staining was used to observe liver injury.Serum iron and total iron binding capacity (TIBC) were detected by colorimetric method.Iron content in liver was observed by Perls’ staining.The protein expressions of divalent metal-ion transporter-1 [(DMT1(+ire),DMT1(-ire)],Ferroportin 1(FPN1),transferrin receptor 1(TfR1),ferritin light chain (FTL),phosphorylation signal transduction and activator of transcription-3 (p-STAT3) and signal transduction and activator of transcription-3 (STAT3) in liver were detected by Western blot.The mRNA expressions of hepcidin,DMT1(+ire),DMT1(-ire),FPN1,TfR1 and interleukin 6 (IL-6) in liver were detected by Q-PCR. Results: Compared with the control group,the structure of liver cells in CIH group was disordered,with fat vacuoles and nuclear atrophy.Compared with the control group,the mRNA and protein expressions of TfR1 and DMT1 (+ire) in CIH group were significantly increased (P<0.05),and protein expressions of membrane FPN1 were significantly decreased (P<0.05).Compared with the control group,the iron deposition in CIH group was significantly increased,the serum iron content and transferrin saturation were significantly decreased (P<0.01),and the expression of FTL protein was significantly increased (P<0.05).Compared with the control group,the mRNA expression of hepcidin and IL-6 in the liver of rats in CIH group was significantly increased (P<0.05),and the ratio of p-STAT3 / STAT3 was increased (P<0.05). Conclusion: CIH exposure may regulate hepcidin-FPN1 system by affecting IL-6/STAT3 pathway,which may cause iron deposition in liver and further aggravate liver injury.
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2023, Vol. 29 
