Circulation：烟酰胺核苷可显著延缓扩张型心肌病小鼠的心脏衰竭进展！

2018-05-24 MedSci MedSci原创

心肌代谢障碍是慢性心力衰竭的一个主要特征。烟酰胺腺嘌呤二核苷酸（NAD+）作为燃料氧化和氧化磷酸化的主要辅酶、酶信号能量应激和氧化应激反应的底物，逐渐成为多种疾病的代谢靶点，包括心衰。但目前对NAD+在心衰中的稳态调控机制知之甚少。为探究NAD+稳态在衰竭的心脏中的潜在变化，Nicolas Diguet等人定量检测NAD+合成酶在人类衰竭心脏的表达水平，同时检测其在敲除心脏的血清反应因子转录因子

心肌代谢障碍是慢性心力衰竭的一个主要特征。烟酰胺腺嘌呤二核苷酸（NAD+）作为燃料氧化和氧化磷酸化的主要辅酶、酶信号能量应激和氧化应激反应的底物，逐渐成为多种疾病的代谢靶点，包括心衰。但目前对NAD+在心衰中的稳态调控机制知之甚少。

为探究NAD+稳态在衰竭的心脏中的潜在变化，Nicolas Diguet等人定量检测NAD+合成酶在人类衰竭心脏的表达水平，同时检测其在敲除心脏的血清反应因子转录因子 (SRFHKO)所诱导的扩张性心肌病（DCM）的小鼠模型的心脏或通过收缩横动脉诱导的心肌肥大的小鼠模型的心脏中的表达水平，来研究NAD+前体供应量对两种小鼠模型的心脏功能的影响。

研究人员观察到在两种小鼠模型的衰竭心脏中，NAD+的表达水平下降30%，伴随回收烟酰胺前体的烟酰胺磷酸核糖基转移酶表达减少，与此同时，催化烟酰胺核苷前体磷酸化的烟酰胺核苷激酶2（KMRK2）表达增多，DCM小鼠的增高水平（40倍）明显高于心肌肥大的小鼠（4倍）。上述变化同样见于人类衰竭心脏的活检组织（与非衰竭对照相比）。研究人员发现Nmrk2基因是一种AMP激活的蛋白激酶、过氧化物酶体增殖激活的受体反应基因，在分离的大鼠心肌中可被能量应激和NAD+衰竭所激活。在FK866-介导的对烟酰胺磷酸化转移酶的抑制作用下，烟酰胺核苷可有效恢复NAD+的合成，并促进心肌细胞进行糖酵解。此外，研究人员还发现饮食补充烟酰胺核苷可通过稳定衰竭心脏的心肌NAD+的水平进而延缓小鼠心衰的进展，该效果在DCM小鼠中尤为明显。烟酰胺核苷治疗还可显著增加已获批用作治疗生物标志物的3种心肌代谢物（烟酸腺嘌呤二核苷酸、甲基烟酰胺和N1-甲基-4-羟基吡啶-5-甲酰胺）的水平。

本研究数据表明烟酰胺核苷，可有效治疗心力衰竭，对于尚无多少治疗选择的扩张型心肌病所导致的心衰疗效尤为显著。

原始出处：

Nicolas Diguet， et al.Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy. Circulation. May 21，2018.https：//doi.org/10.1161/CIRCULATIONAHA.116.026099

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2018-07-01 lsj637

#扩张#

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2018-10-12 chenlianhui

#烟酰胺核苷#

44 0
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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=318259, encodeId=ac7c31825984, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Thu May 24 22:52:48 CST 2018, time=2018-05-24, status=1, ipAttribution=)]
2018-05-31 半夏微凉

学习了谢谢分享

62 0
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2018-05-28 大爰

好文章学习并分享!!

72 0
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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=318259, encodeId=ac7c31825984, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Thu May 24 22:52:48 CST 2018, time=2018-05-24, status=1, ipAttribution=)]
2018-05-27 大爰

学习了谢谢分享!!

68 0
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2018-05-26 zhouqu_8

#心脏衰竭#

43 0
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2018-05-26 爆笑小医

#肌病#

34 0
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2018-05-25 cscdliu

学习了.谢谢

76 0
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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=318259, encodeId=ac7c31825984, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Thu May 24 22:52:48 CST 2018, time=2018-05-24, status=1, ipAttribution=)]
2018-05-24 天地飞扬

了解一下.谢谢分享!

76 0
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GetPortalCommentsPageByObjectIdResponse(id=318416, encodeId=9d65318416b3, content=学习了.谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/10/23/557c1f19aaf5459a8405411e38903c4b.jpg, createdBy=dfc02088287, createdName=cscdliu, createdTime=Fri May 25 10:03:47 CST 2018, time=2018-05-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=318263, encodeId=9c3a318263bd, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu May 24 23:13:14 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=318259, encodeId=ac7c31825984, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Thu May 24 22:52:48 CST 2018, time=2018-05-24, status=1, ipAttribution=)]
2018-05-24 wqkm

^_^^_^^_^

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