Wang Li, Zheng Quan, Yuan Yadong, Li Yanpeng, Gong Xiaowei
Department of Respiratory Disease and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Exp Ther Med. 2017 May;13(5):2537-2543. doi: 10.3892/etm.2017.4243. Epub 2017 Mar 20.
The present study aimed to investigate the effects of 17β-estradiol (E2) and 2-methoxyestradiol (2ME) on the oxidative stress-hypoxia inducible factor-1 (OS-HIF-1) pathway in hypoxic pulmonary hypertensive rats. Female Sprague-Dawley rats were divided randomly into 4 groups, as follows: i) Control (Group A); ii) ovariectomy (OVX) + hypoxia (Group B); iii) OVX + hypoxia + E2 injection (Group C); and iv) 2ME injection (Group D). The rats were maintained under hypoxic conditions for 8 weeks, and mean pulmonary artery pressure (mPAP) and pulmonary arteriole morphology were measured. The reactive oxygen species, superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (Cu/ZnSOD) levels in serum were also measured. MnSOD and HIF-1α expression levels in lung tissue were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. The mPAP and arterial remodeling index were significantly elevated following chronic hypoxia exposure; however, experimental data revealed a reduced response in E2 and 2ME intervention rats. Compared with Group A, Group B had significantly elevated oxidative stress levels, as illustrated by increased serum ROS levels, decreased serum SOD and MnSOD levels and decreased MnSOD mRNA and protein expression levels in lung tissue. Furthermore, HIF-1α mRNA and protein expression in Group B was significantly elevated compared with Group A. E2 and 2ME intervention significantly attenuated the aforementioned parameter changes, suggesting that E2 and 2ME partially ameliorate hypoxic pulmonary hypertension. The underlying mechanism of this may be associated with the increase in MnSOD activity and expression and reduction in ROS level, which reduces the levels of transcription and translation of HIF-1α.
本研究旨在探讨17β-雌二醇（E2）和2-甲氧基雌二醇（2ME）对低氧性肺动脉高压大鼠氧化应激-缺氧诱导因子-1（OS-HIF-1）通路的影响。将雌性Sprague-Dawley大鼠随机分为4组，如下：i）对照组（A组）；ii）卵巢切除术（OVX）+低氧组（B组）；iii）OVX+低氧+E2注射组（C组）；iv）2ME注射组（D组）。将大鼠置于低氧条件下饲养8周，测量平均肺动脉压（mPAP）和肺小动脉形态。还检测了血清中的活性氧、超氧化物歧化酶（SOD）、锰超氧化物歧化酶（MnSOD）和铜锌超氧化物歧化酶（Cu/ZnSOD）水平。通过蛋白质印迹法和逆转录-定量聚合酶链反应测定肺组织中MnSOD和HIF-1α的表达水平。慢性低氧暴露后，mPAP和动脉重塑指数显著升高；然而，实验数据显示E2和2ME干预组大鼠的反应减弱。与A组相比，B组氧化应激水平显著升高，表现为血清ROS水平升高、血清SOD和MnSOD水平降低以及肺组织中MnSOD mRNA和蛋白表达水平降低。此外，与A组相比，B组中HIF-1α mRNA和蛋白表达显著升高。E2和2ME干预显著减轻了上述参数变化，表明E2和2ME可部分改善低氧性肺动脉高压。其潜在机制可能与MnSOD活性和表达增加以及ROS水平降低有关，从而降低了HIF-1α的转录和翻译水平。
