| ObjectiveHypoxia inducible factor-1 (HIF-1) is an important transcription factor which mediate mammalian cells to adapt to hypoxia. The expression of more than 40 genes responsible for angiogenesis, glycolysis, and the inhibition of apoptosis are regulated by HIF-1. However , the effect of hypoxic preconditioning on HAPE is not fully elucidated and the effect of HIF-1 on hypoxic preconditioning in lungs is unknown. The objective of the present research was to investigate how hypoxic preconditioning affect HAPE in rats and the changes of HIF-1 a expression in hypoxic preconditioning. We also studied the effect of one of known HIF-1 a inducers, desferrioxamine(DFX), on HIF-1 a expression and protection rats from HAPE in order to explore the possibility of substitution DFX for hypoxic preconditioning. MethodsThe study consisted of two parts. Rats exposed to simulated altitude of 6000m for 24 hours was used as HAPE animal model.Part one, healthy male and female Wistar rats(n=56) were randomly divided into 7 groups: normal control group( N, n=8), acute hypoxic control group(Ho, n=8), acute hypoxic group(Hi, n=8), 3000m hypoxic preconditioning control group(C3.o, n=8), 3000m hypoxic preconditioning group(C3.1, n=8), 5000m hypoxic preconditioning control group(C5.0, n=8) and 5000m hypoxic preconditioning group(C5.1, n=8) . At the end of treatment, all animals were anesthetized and their lungs were removed. Western blot and RT-PCR were employed to examined the changes of HIF-1 a expression in lungs of N group, HO group, C3.o group and C5.0 group. Microstructure and ultrastructure of lung tissue in N group, H1 group, C3.1 group and C5.1 group were also observed.Part two, to study the effect of DFX on HIF-1 a expression in rats lung, 25 healthy male and female Wistar rats were administered a single intraperitoneal injection of DFX solution(200mg/kg), immunohistochemistery and RT-PCR analysis was performed to examine HIF-1 a expression on lungs at either 0 (n=5), 2(n=5), 4(n=5), 8(n=5), or 24(n=5) hours after DFX administration. To investigate whether DFX preconditioning in rats produced lung protection similar to hypoxic preconditioning, 40 Wistar rats were randomly divided into 5 groups: normal control group(N, n=8), acute hypoxic control group(Ho,n=8) , acute hypoxic group(H), n=8) , DFX preconditioning control group(DFXo, n=8) and DFX preconditioning group(DFXj, n=8). At the end of treatment, all animals were anesthetized and their lungs were removed. RT-PCR was employed to examined the changes of HIF-1 a mRNA expression in lungs of N group, HO group, DFXo group, Microstructure and ultrastructure of lung tissue in N group, HI group, DFXi group were observed, and the changes of NO content and Na+ - K+ ATPase activity in lung were measured either. Results:1. Pulmonary interstitial edema was found in rats exposed to simulated altitude of 6000m for 24 hours directly by light microscope and electron microscope. As compared with acute hypoxia group, pulmonary edema was relieved after hypoxic preconditioning or DFX preconditioning.2. Levels of HIF-1 a mRNA expression increased when hypoxic preconditioning was deepened. While HIF-1 a proteins can not be detected in all groups of rat lung tissue by Western blot analysis.3. HIF-1 a mRNA was constitutively expressed at a low but detectable level in lung. After treated with DFX(200mg/kg), HIF-1 a mRNA levels in lung was markedly elevated at 2 hour and peaked at 4 hour and gradually return to the normal level at 24 hour. The expression of HIF-1 a mRNA in DFXo group was significantly higher than in HO group.4. As compared with control group, NO content in lung tissue was markedly decreased in H1 group. While NO content in DFXi group was much higher than in HI group, but it did not retrieve to the normal level.5. Na+-K+ ATPase activity in lung was markedly decreased in HI group compared with N group. While Na+- K+ ATPase activity was significantly higher in DFXi group than in N group. Conclusion1. We successfully es...
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