Circulation :非那雄胺(抗雄激素治疗):为心衰治疗提供新思路

2015-02-02 MedSci MedSci原创

目前慢性心衰治疗的患者,死亡率仍旧居高不减,然而,人们却往往忽视了一个重要的差别,那就是女性心衰患者相对于男性而言,死亡率要来的低。性激素或许可以为这个差别作出一定的解释,尤其是雄激素和雌激素在心衰患者中的表达,暗示着两者可能直接作用于心肌。 5α-还原酶能够将睾酮转换成二氢睾酮(其作用是睾酮的10倍),而非那雄胺能够抑制5α-还原酶。德国汉诺威医学院Zwadlo C等人研究了非那雄

目前慢性心衰治疗的患者,死亡率仍旧居高不减,然而,人们却往往忽视了一个重要的差别,那就是女性心衰患者相对于男性而言,死亡率要来的低。性激素或许可以为这个差别作出一定的解释,尤其是雄激素和雌激素在心衰患者中的表达,暗示着两者可能直接作用于心肌。
 
5α-还原酶能够将睾酮转换成二氢睾酮(其作用是睾酮的10倍),而非那雄胺能够抑制5α-还原酶。德国汉诺威医学院Zwadlo C等人研究了非那雄胺对心衰患者中的疗效,探索非那雄胺是否可以对心衰患者有着治疗意义,其研究成果发表在1月份circulation期刊上。
 
背景:女性患者在患有主动脉瓣狭窄,肥厚性心肌病,或者心衰后,其预后要比男性患者好。目前已有的数据提示,主要是雄激素(睾酮,双氢睾酮)对心肌肥厚以及心衰起到了一定的作用。因此,研究分析了抗雄激素药物非那雄胺(通过5α-还原酶抑制双氢睾酮的产生)治疗,能够改善病理性心室重构以及改善心衰。
 
方法和结果:
研究发现,双氢睾酮相关的心脏病理性肥大的小鼠和人,其5α-还原酶的3中亚型表达显著增加。主动脉收缩增加持续1周后,对小鼠进行为期2周的非那雄胺治疗。非那雄胺治疗后,心脏功能,心肌肥厚,心脏扩大,以及心肌纤维化在雌性和雄性小鼠中都有明显改善。另外,非那雄胺能改善长期血压超负荷小鼠的心脏功能和减少其死亡率,预防心肌Gαq高表达心肌病小鼠的疾病发展。分子机制研究结果表明,在离体心肌细胞中,非那雄胺能够通过减少双氢睾酮从而抑制心肌肥厚和Akt依赖的心肌肥厚的发展,而引入活化的Akt会减弱非那雄胺的这些效应。
 
结论:非那雄胺,目前被用于治疗前列腺疾病,能够有效地逆转小鼠心肌肥厚和心脏功能缺失,可能为心衰患者提供一种新的治疗思路。

原文出处:
 
Zwadlo C, Schmidtmann E, Szaroszyk M, Kattih B, Froese N, Hinz H, Schmitto JD, Widder J, Batkai S, Bahre H, Kaever V, Thum T, Bauersachs J, Heineke J. Anti-Androgenic Therapy with Finasteride Attenuates Cardiac Hypertrophy and Left Ventricular Dysfunction. Circulation. 2015.

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    2015-09-03 晓辰
  2. [GetPortalCommentsPageByObjectIdResponse(id=2019285, encodeId=23a420192852c, content=<a href='/topic/show?id=61f458359f7' target=_blank style='color:#2F92EE;'>#新思路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58359, encryptionId=61f458359f7, topicName=新思路)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5712500001, createdName=晓辰, createdTime=Thu Sep 03 03:12:00 CST 2015, time=2015-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=17847, encodeId=6c961e8471a, content=新思路,心衰患者的治疗又多一个选择。, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2b7c1616875, createdName=Jenner77, createdTime=Fri Mar 06 22:38:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16462, encodeId=8bcd16462bb, content=明白, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200609/ef6a57dbe7f1489dad7446b7c5217858/d5e4fe65996c4446a029b0f5d056abb1.jpg, createdBy=6b011518214, createdName=午夜星河, createdTime=Thu Feb 19 13:02:00 CST 2015, time=2015-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16209, encodeId=14cd162093d, content=已阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=138, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da6b7222, createdName=chinayinhan, createdTime=Tue Feb 17 00:56:00 CST 2015, time=2015-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1307339, encodeId=50d9130e33907, content=<a href='/topic/show?id=b1d766836e4' target=_blank style='color:#2F92EE;'>#激素治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66836, encryptionId=b1d766836e4, topicName=激素治疗)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bfa6343, createdName=aliceclz, createdTime=Wed Feb 04 00:12:00 CST 2015, time=2015-02-04, status=1, ipAttribution=)]
    2015-03-06 Jenner77

    新思路,心衰患者的治疗又多一个选择。

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2019285, encodeId=23a420192852c, content=<a href='/topic/show?id=61f458359f7' target=_blank style='color:#2F92EE;'>#新思路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58359, encryptionId=61f458359f7, topicName=新思路)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5712500001, createdName=晓辰, createdTime=Thu Sep 03 03:12:00 CST 2015, time=2015-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=17847, encodeId=6c961e8471a, content=新思路,心衰患者的治疗又多一个选择。, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2b7c1616875, createdName=Jenner77, createdTime=Fri Mar 06 22:38:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16462, encodeId=8bcd16462bb, content=明白, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200609/ef6a57dbe7f1489dad7446b7c5217858/d5e4fe65996c4446a029b0f5d056abb1.jpg, createdBy=6b011518214, createdName=午夜星河, createdTime=Thu Feb 19 13:02:00 CST 2015, time=2015-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16209, encodeId=14cd162093d, content=已阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=138, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da6b7222, createdName=chinayinhan, createdTime=Tue Feb 17 00:56:00 CST 2015, time=2015-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1307339, encodeId=50d9130e33907, content=<a href='/topic/show?id=b1d766836e4' target=_blank style='color:#2F92EE;'>#激素治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66836, encryptionId=b1d766836e4, topicName=激素治疗)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bfa6343, createdName=aliceclz, createdTime=Wed Feb 04 00:12:00 CST 2015, time=2015-02-04, status=1, ipAttribution=)]
    2015-02-19 午夜星河

    明白

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2019285, encodeId=23a420192852c, content=<a href='/topic/show?id=61f458359f7' target=_blank style='color:#2F92EE;'>#新思路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58359, encryptionId=61f458359f7, topicName=新思路)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5712500001, createdName=晓辰, createdTime=Thu Sep 03 03:12:00 CST 2015, time=2015-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=17847, encodeId=6c961e8471a, content=新思路,心衰患者的治疗又多一个选择。, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2b7c1616875, createdName=Jenner77, createdTime=Fri Mar 06 22:38:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16462, encodeId=8bcd16462bb, content=明白, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200609/ef6a57dbe7f1489dad7446b7c5217858/d5e4fe65996c4446a029b0f5d056abb1.jpg, createdBy=6b011518214, createdName=午夜星河, createdTime=Thu Feb 19 13:02:00 CST 2015, time=2015-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16209, encodeId=14cd162093d, content=已阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=138, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da6b7222, createdName=chinayinhan, createdTime=Tue Feb 17 00:56:00 CST 2015, time=2015-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1307339, encodeId=50d9130e33907, content=<a href='/topic/show?id=b1d766836e4' target=_blank style='color:#2F92EE;'>#激素治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66836, encryptionId=b1d766836e4, topicName=激素治疗)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bfa6343, createdName=aliceclz, createdTime=Wed Feb 04 00:12:00 CST 2015, time=2015-02-04, status=1, ipAttribution=)]
    2015-02-17 chinayinhan

    已阅

    0

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