摘要

BACKGROUND:In comparison with men, women have a better prognosis when experiencing aortic valve stenosis, hypertrophic cardiomyopathy, or heart failure. Recent data suggest that androgens like testosterone or the more potent dihydrotestosterone contribute to the development of cardiac hypertrophy and failure. Therefore, we analyzed whether antiandrogenic therapy with finasteride, which inhibits the generation of dihydrotestosterone by the enzyme 5-α-reductase, improves pathological ventricular remodeling and heart failure.
METHODS AND RESULTS:We found a strongly induced expression of all 3 isoforms of the 5-α-reductase (Srd5a1 to Srd5a3) in human and mouse hearts with pathological hypertrophy, which was associated with increased myocardial accumulation of dihydrotestosterone. Starting 1 week after the induction of pressure overload by transaortic constriction, mice were treated with finasteride for 2 weeks. Cardiac function, hypertrophy, dilation, and fibrosis were markedly improved in response to finasteride treatment in not only male, but also in female mice. In addition, finasteride also very effectively improved cardiac function and mortality after long-term pressure overload and prevented disease progression in cardiomyopathic mice with myocardial Gαq overexpression. Mechanistically, finasteride, by decreasing dihydrotestosterone, potently inhibited hypertrophy and Akt-dependent prohypertrophic signaling in isolated cardiac myocytes, whereas the introduction of constitutively active Akt blunted these effects of finasteride.
CONCLUSIONS:Finasteride, which is currently used in patients to treat prostate disease, potently reverses pathological cardiac hypertrophy and dysfunction in mice and might be a therapeutic option for heart failure.

译文

背景: 与男性相比,女性在主动脉瓣狭窄、肥厚型心肌病或心力衰竭时预后更好。最近的数据表明,像睾酮或更有效的二氢睾酮这样的雄激素会导致心肌肥厚和衰竭。因此,我们分析了非那雄胺的抗雄激素治疗是否改善了病理性心室重构和心力衰竭,非那雄胺抑制了 5-α 还原酶产生的双氢睾酮。
方法和结果: 我们发现 5-α 还原酶的所有 3 种亚型 (Srd5a1 到 Srd5a3) 在患有病理性肥大的人和小鼠心脏中都有强烈诱导表达, 这与双氢睾酮的心肌蓄积增加有关。经主动脉缩窄诱导压力超负荷后 1 周开始,小鼠接受非那雄胺治疗 2 周。非那雄胺治疗不仅对雄性小鼠,而且对雌性小鼠的心脏功能、肥大、扩张和纤维化也有显著改善。此外,非那雄胺还非常有效地改善了长期压力超负荷后的心脏功能和死亡率,并阻止了心肌 g α q 过表达的心肌病小鼠的疾病进展。从机制上讲,非那雄胺通过降低双氢睾酮,有效抑制离体心肌细胞的肥大和 Akt 依赖性的促肥厚信号,而组成性活性 Akt 的引入减弱了非那雄胺的这些作用。
结论: 非那雄胺目前用于治疗前列腺疾病,有效逆转小鼠病理性心肌肥厚和功能障碍,可能是心力衰竭的治疗选择。

Finasteride

内分泌 前列腺肥大 治疗药物
概述  :  

基本信息主要用于治疗男性前列腺肥大或脱发,也可用于治疗毛发过度生长,也用于变性女性。它的副作用一般是轻微的,有些男人会出现性功能障碍,沮丧,焦虑或乳房增大。它也可能增加某些形式的前列腺癌的风险,非那雄胺是5α-还原酶抑制剂,因此可用来拮抗雄激素。临床应用非那雄胺治疗良性前列腺增生(BPH),也称为前列腺肥大。非那雄胺可能会改善与BPH相关的症状,如排尿困难,夜间起床排尿,排尿开始和结束时排尿困难以及尿流减少。有症状的益处主要见于前列腺体积>40 cm3的患者。在长期研究中,非那雄胺可降低急性尿潴

Finasteride

释    义   n. 非那雄胺

例    句   Objective To establish the determination method of the assay and content uniformity for finasteride tablets by HPLC. 目的探讨用高效液相色谱法测定非那雄胺片的含量及含量均匀度。

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