Beneficial effect of dehydroepiandrosterone on pulmonary hypertension in a rodent model of pulmonary hypertension in infants
Beneficial effect of dehydroepiandrosterone on pulmonary hypertension in a rodent model of pulmonary hypertension in infants
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DOI：
10.1038/pr.2013.73
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发表时间：
2013-08-01
影响因子：
3.6
通讯作者：
Savineau, Jean-Pierre
中科院分区：
文献类型：
--
作者：
de la Roque, Eric Dumas;Quignard, Jean-Francois;Savineau, Jean-Pierre
背景：肺动脉高压（PH）是一种影响成人或婴儿人群的疾病。脱氢表雄酮（DHEA）是一种类固醇激素，以前已被证明可以预防和逆转成年大鼠模型中的PH。因此，我们研究了其在慢性缺氧PH大鼠模型中的作用。方法：动物在低压舱中维持3周以诱导PH，伴随或不伴随DHEA治疗（每隔一天30 mg/kg）。DHEA显著降低平均肺动脉压（通过右心导管术测量），肺动脉重塑（通过组织学评估）和右心室肥大（通过回波描记术和富尔顿指数测量）。在肺动脉平滑肌细胞（PASMC）水平，DHEA增加大电导钙激活钾通道（BKCa）的活性和表达（通过膜片钳技术评估）。DHEA还抑制血清素和氯化钾诱导的收缩和平滑肌细胞proliferation.CONCLUSION：总的来说，这些结果表明，DHEA防止PH在婴儿大鼠，因此可能是临床相关的管理PH在人类婴儿。
BACKGROUND: Pulmonary hypertension (PH) is a disease that affects the adult or infant population. Dehydroepiandrosterone (DHEA), a steroid hormone, has been previously shown to prevent and to reverse PH in an adult rat model. We thus investigated its effect in a rat-pup model of chronic hypoxic PH.METHODS: Animals were maintained for 3 wk in a hypobaric chamber to induce PH, with or without concomitant treatment with DHEA (30 mg/kg every alternate day).RESULTS: DHEA significantly reduced mean pulmonary artery pressure (measured by right cardiac catheterization), pulmonary artery remodeling (evaluated by histology), and right-ventricular hypertrophy (measured by echography and by the Fulton index). At the level of the pulmonary artery smooth muscle cell (PASMC), DHEA increased activity and expression of the large-conductance Ca2+-activated potassium channel (BKCa) (assessed by means of the patch clamp technique). DHEA also inhibited both serotonin- and KCI-induced contraction and smooth muscle cell proliferation.CONCLUSION: Collectively, these results indicate that DHEA prevents PH in infant rats and may therefore be clinically relevant for the management of PH in human infants.