Effect of Estradiol and its Metabolite on Hypoxic Induced Factor-1αand Alkane Hydroxylase in Experimental Rats With Ovariectomy and Hypoxic Pulmonary Hypertension / 中国循环杂志

ABSTRACT

Objective: To explore the effects of 17 β-estrogen (E2) and 2-methoxyestradiol (2ME) on hypoxic induced factor-1α (HIF-1α) and alkane hydroxylase (AlkB) in experimental rats with ovariectomy and hypoxic pulmonary hypertension. Methods: A total of 60 healthy female SD rats with castrated surgery were randomly divided into 6 groups①Routine oxygen group,②Routine oxygen + E2 group, the rats received subcutaneous injection of E2 (20 μg/kg?d),③Routine oxygen + 2ME group, the rats received 2ME (240 μg/kg?d) and④Hypoxia group,⑤Hypoxia + E2 group,⑥Hypoxia + 2ME group.n=10 in each group and all animals were treated for 8 weeks to establish the hypoxic pulmonary hypertension model. The mean pulmonary artery pressure (mPAP) was measured after bloodletting, right ventricle hypertrophy index (RVHI) was calculated and small pulmonary artery remodeling was observed by HE staining. The expression level of HIF-1α and AlkB were examined by RT-PCR and Western blot analysis. Results: Compared with Routine oxygen group, the rats in Hypoxia group had obviously thickened small pulmonary artery wall with narrowed lumen, increased mPAP and RVHI; the above changes in Hypoxia + E2 and Hypoxia + 2ME groups were relatively smaller, their mPAP and RVHI were higher than Routine oxygen group, while mPAP and RVHI were similar between Hypoxia + E2 and Hypoxia + 2ME groups. There were no real morphological changes in small pulmonary vessels in Routine oxygen + E2 and Routine oxygen + 2ME groups. The HIF-1α expression was obviously elevated in Hypoxia group than Routine oxygen group, while the elevation was less in Hypoxia + E2 and Hypoxia + 2ME groups. HIF-1α expression had no real changes in Routine oxygen+E2 and Routine oxygen + 2ME groups. The AlkB expression was obviously reduced in Hypoxia group than Routine oxygen group, while the reduction was less in Hypoxia + E2 and Hypoxia + 2ME groups. AlkB expression had no real changes in Routine oxygen + E2 and Routine oxygen + 2ME groups. Conclusion: Estradiol E2 and 2ME could remit pulmonary hypertension which might be via up-regulating AlkB expression and down-regulating HIF-1α expression in experimental rats with hypoxic pulmonary hypertension.