EUR RESPIR J: 利用雌激素抑制剂治疗肺动脉高压

2017-08-19 MedSci MedSci原创

女性性别因素是多种肺动脉高压(PAH)最强烈的流行病学风险因素。雌性激素的增加会使女性患上PAH的几率增加三倍,最终导致右心衰竭和死亡。受体BMPR2的突变导致一种可遗传的PAH, BMPR2突变小鼠自发地形成这种疾病。雌激素增加了外显率(产生PAH的小鼠的百分比)和疾病的严重程度。詹姆斯·韦斯特(James West)博士和他的同事用雌激素抑制剂anastrozole、fulvestrant和t


女性性别因素是多种肺动脉高压(PAH)最强烈的流行病学风险因素。雌性激素的增加会使女性患上PAH的几率增加三倍,最终导致右心衰竭和死亡。

受体BMPR2的突变导致一种可遗传的PAH, BMPR2突变小鼠自发地形成这种疾病。雌激素增加了外显率(产生PAH的小鼠的百分比)和疾病的严重程度。

詹姆斯·韦斯特(James West)博士和他的同事用雌激素抑制剂anastrozole、fulvestrant和tamoxifen治疗BMPR2突变小鼠。此外,分别将BMPR2突变小鼠的雌激素受体(ESR)1和ESR2敲除,以评估受体特异性。并且测量其血液动力学和代谢结果。他们发现,雌激素抑制对BMPR2突变的PAH小鼠具有预防和治疗作用,与氧化脂质形成和胰岛素抵抗代谢缺陷的减少有关。虽然fulvestrant和anastrozole比tamoxifen更有效,但tamoxifen可能对绝经前女性更有用,因为它降低了更年期诱导的风险。

该研究发表在《欧洲呼吸杂志》上,结果显示,可以通过纠正代谢缺陷抑制雌激素水平从而改善肺血管疾病。基于这些研究,最近美国国立卫生研究院(NIH)批准并资助了雌激素抑制人类PAH的临床试验。

原文出处:Xinping Chen et al. Oestrogen inhibition reverses pulmonary arterial hypertension and associated metabolic defects, European Respiratory Journal (2017).

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    2018-01-30 jklm09
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    2017-08-20 184****9840

    学习了谢谢分享

    0

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    2017-08-19 131****1460

    学习了受益匪浅。

    0

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    2017-08-19 ishtar

    到底是激素还是BMPR2导致PAH

    0