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Stroke：可溶性FLT1基因治疗可以减轻脑动静脉畸形的严重程度

2017-03-22 xing.T MedSci原创

sFLT1bAVM基因治疗
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通过调节机制来限制sFLT1在bAVM中的表达，AAV9-sFLT1可以发展成为一个更安全的治疗以减少bAVM严重。

大脑动静脉畸形（bAVM）是颅内出血的重要危险因素。当前的治疗方法与高发病率相关，过度的血管内皮生长因子可能参与了bAVM的病理生理学。因为可溶性FLT1与血管内皮生长因子结合且具有很高的亲和力，近日，卒中领域权威杂志Stroke上发表了一篇研究文章，研究人员验证了通过静脉输入腺相关病毒载体血清型-9表达可溶性FLT1（AAV9-sFLT1）可以缓解bAVM的表型。

研究人员采用了两种小鼠模型。在模型1中，在R26CreER小鼠诱导bAVM；Eng2f/2f小鼠通过全身Eng基因敲除和大脑局灶性脑血管刺激；在模型诱导的时间将AAV2-sFLT02（AAV表达更短的sFLT1）注射入脑内，8周后静脉注射AAV9-sFLT1。在模型2中，SM22αCre；Eng2f/2f小鼠在5周龄有90%发生自发性的bAVM在6周时有50%的死亡率；AAV9-sFLT1通过静脉输送到4至5周龄的小鼠。在AAV9-sFLT1输入4周后和收集组织标本。

研究人员发现AAV2-sFLT02可以抑制bAVM的形成，并且AAV9-sFLT1可以减少模型1动物的血管异常（GFP与sFlt1：3.66±1.58/200血管 vs. 1.98±1.29，P＜0.05）。在模型2的小鼠中，AAV9-sFLT1可以减少bAVM的发生（GFP与sFLT1：100% vs. 36%）和死亡率（GFP与sFLT1：57% [12/22小鼠] vs. 24% [4/19小鼠]，P＜0.05）。肾、肝功能无明显变化。在接受AAV9-sFLT1处理的模型1小鼠中56%的小鼠存在轻微的肝脏炎症。

通过调节机制来限制sFLT1在bAVM中的表达，AAV9-sFLT1可以发展成为一个更安全的治疗以减少bAVM严重。         

原始出处：

Wan Zhu, et al. Soluble FLT1 Gene Therapy Alleviates Brain Arteriovenous Malformation Severity.Stroke. 2017.https://doi.org/10.1161/STROKEAHA.116.015713

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    2017-10-17 12498cf9m42(暂无昵称)

    #动静脉畸形#

    0

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    2017-07-30 fusion

    #静脉#

    0

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    2017-06-09 1e145228m78(暂无匿称)

    学习了，谢谢作者分享!

    0

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    2017-03-24 wushaoling

    #畸形#

    0

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    2017-03-23 1e0ece0dm09(暂无匿称)

    谢谢

    0

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    2017-03-23 嘿嘿哈哈嗯

    不错，学习了

    0

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    2017-03-23 虈亣靌

    很好，学习值得分享！

    0

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    2017-03-22 万里江山一孤舟

    学习了

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1642127, encodeId=c609164212e74, content=<a href='/topic/show?id=5070333625b' target=_blank style='color:#2F92EE;'>#动静脉畸形#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33362, encryptionId=5070333625b, topicName=动静脉畸形)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=46c022864035, createdName=12498cf9m42(暂无昵称), createdTime=Tue Oct 17 06:58:00 CST 2017, time=2017-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1697426, encodeId=7bb2169e4268b, content=<a href='/topic/show?id=f2399910109' target=_blank style='color:#2F92EE;'>#静脉#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99101, encryptionId=f2399910109, topicName=静脉)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0bc129907796, createdName=fusion, createdTime=Sun Jul 30 01:58:00 CST 2017, time=2017-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=208724, encodeId=335e208e240d, content=学习了，谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Fri Jun 09 22:45:42 CST 2017, time=2017-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1362161, encodeId=76eb136216195, content=<a href='/topic/show?id=9857e03444b' target=_blank style='color:#2F92EE;'>#畸形#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70344, encryptionId=9857e03444b, topicName=畸形)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca20190, createdName=wushaoling, createdTime=Fri Mar 24 02:58:00 CST 2017, time=2017-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=182157, encodeId=5dff18215eaf, content=谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5K46ZAxBHmHsph32KkfsWGwmickB6RsCUD8KruE4vo5CpvXfdu16GBpp4ibh6WJu1o9iatP1LWKDmvmic/0, createdBy=be6f1940165, createdName=1e0ece0dm09(暂无匿称), createdTime=Thu Mar 23 11:46:08 CST 2017, time=2017-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=182040, encodeId=a1de18204060, content=不错，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9b5f2039852, createdName=嘿嘿哈哈嗯, createdTime=Thu Mar 23 00:58:28 CST 2017, time=2017-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=182028, encodeId=20f218202803, content=很好，学习值得分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Thu Mar 23 00:14:10 CST 2017, time=2017-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=181955, encodeId=78201819555f, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/03/22/9492b0bdd3ebdf662ab1cde6e8473dca.jpg, createdBy=0f261679513, createdName=万里江山一孤舟, createdTime=Wed Mar 22 13:16:14 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=181944, encodeId=2ed31819448d, content=很好的学习资料，谢谢了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161026/IMG58107C0F82E499574.jpg, createdBy=00e81970035, createdName=1e15b6fem30(暂无匿称), createdTime=Wed Mar 22 12:53:43 CST 2017, time=2017-03-22, status=1, ipAttribution=)]
    2017-03-22 1e15b6fem30(暂无匿称)

    很好的学习资料，谢谢了。

    0