JCI:高血压是如何与阿兹海默病发生联系的?

2016-12-08 学术经纬 学术经纬

高血压是全球影响范围最广的疾病之一。在人体中,大脑是高血压影响的主要器官之一。众所周知,高血压是中风发生的一个主要诱因。除此之外,高血压也会影响到大脑的认知功能。近年来,人们越发地意识到高血压和阿兹海默病之间的密切联系。最近,位于纽约的费尔家族大脑与思维研究所(Feil Family Brain and Mind Research Institute)的研究人员在《the Journal of C

高血压是全球影响范围最广的疾病之一。在人体中,大脑是高血压影响的主要器官之一。众所周知,高血压是中风发生的一个主要诱因。除此之外,高血压也会影响到大脑的认知功能。近年来,人们越发地意识到高血压和阿兹海默病之间的密切联系。

最近,位于纽约的费尔家族大脑与思维研究所(Feil Family Brain and Mind Research Institute)的研究人员在《the Journal of Clinical Investigation》上发表文章,揭示了高血压影响大脑中的神经血管调节和认知机能的机理,发现了血管周巨噬细胞(perivascular macrophage, PVM)在这一过程中的关键作用。

▲文章通讯作者Costantino Ladecola教授

(图片来源:Feil Family Brain and Mind Research Institute)

脑血管系统的健康对于大脑至关重要。大脑内没有能量储备,必需依赖血液循环系统时刻保证能量供应。当大脑活动增加时,神经元、神经胶质细胞、血管壁细胞等构成的神经血管单元,会通过神经血管耦合机制增加脑血管流量,以满足大脑升高的代谢需要;同时,血管内皮细胞调节着血脑屏障的通透性,并控制血管活性物质的释放,以调节局部脑血流量。上述神经血管调节机制对于维持脑部微环境的内稳态至关重要。

然而,当高血压发生时,上述调节机制便会出现异常,从而可能导致脑细胞受损。血管紧张素II(ANGII)是一种可升高血压的血管活性物质,与高血压的发生密切相关,因此也成为了高血压的治疗靶点之一。之前研究已显示,在小鼠中长时间(14天)灌注ANGII可造成血压的缓慢增加(以模拟高血压的情形),并造成脑部神经血管调节机制失常,而后者则可能会影响到大脑认知功能。

▲脑血管横截面电镜切片,示血管周巨噬细胞

(图片来源:《the Journal of Clinical Investigation》)

研究者发现,血管周巨噬细胞在上述机能改变中发挥有重要作用,是ANGII引起神经血管调节机制失常所必需的。当小鼠被长时间灌注ANGII后,ANGII可穿过血脑屏障,进入血管周围空间。这时,ANGII可结合血管周巨噬细胞表面的ANGII一型受体(AT1R),使后者可激活NOX2型NADPH氧化酶,进而催化产生活性氧自由基(ROS),造成已知可损害脑部神经血管调节机制的氧化胁迫。相比之下,短时间的快速灌注无法使ANGII穿过血脑屏障。

▲NADPH氧化酶催化生成ROS(图片来源:wikiwand)

为了更好地模拟人类高血压的情形,研究者采用了慢性高血压小鼠模型株BPH/2J进行实验,这类小鼠具有明显的脑部神经血管调节机制异常和认知功能障碍。结果显示,当血管周巨噬细胞被氯膦酸盐(clodronate)清除、其AT1R被阻断或ROS被清除后,神经血管调节机制的异常会显著减轻;血管周巨噬细胞的清除更是会显著改善小鼠的认知功能。

▲ANGII对神经血管调节的影响

(图片来源:《the Journal of Clinical Investigation》)

这一研究显示,血管周巨噬细胞在高血压的情形下可发生造成氧化胁迫的炎症反应,引起脑部神经血管调节机制和大脑认知功能的异常,并提示了血管周巨噬细胞作为药物靶点的潜质,有望用于减轻大脑机能因高血压而受到的损害。

原始出处:

[1]Giuseppe Faraco,et al. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J CLIN INVEST.November 14, 2016.

[2] NADPH oxidase: Wikipedia

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    2016-12-18 李东泽

    很好,不错,以后会多学习

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1735468, encodeId=a76e1e3546885, content=<a href='/topic/show?id=7f019e71750' target=_blank style='color:#2F92EE;'>#阿兹海默病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97717, encryptionId=7f019e71750, topicName=阿兹海默病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ff833907849, createdName=xre2019, createdTime=Mon Feb 13 11:52:00 CST 2017, time=2017-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1982039, encodeId=976c198203902, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Sat Mar 11 20:52:00 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=163810, encodeId=870116381093, content=很好,不错,以后会多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzUn81b5CF5ibVPib8jWI92iciaxmqGHlwruOnK4SVZykd4iahqo1hicklIibyZoxm55X7EM8BW9eX1h1hQ2/0, createdBy=8aa81937526, createdName=李东泽, createdTime=Sun Dec 18 15:25:03 CST 2016, time=2016-12-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=163197, encodeId=d00916319e36, content=高血压很多人都有,但是AD还是少数,, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29ab1719082, createdName=MyQueen, createdTime=Fri Dec 16 08:37:45 CST 2016, time=2016-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=161315, encodeId=61a2161315bf, content=每天吃20克坚果能降低多种疾病风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Thu Dec 08 23:23:57 CST 2016, time=2016-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=161314, encodeId=2b0d1613146d, content=每天吃20克坚果能降低多种疾病风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Thu Dec 08 23:23:50 CST 2016, time=2016-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=161229, encodeId=6319161229c0, content=学习了很多先进的医学知识讲座, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161027/IMG58114E1818EA51495.jpg, createdBy=4b2c1959822, createdName=雅文博武, createdTime=Thu Dec 08 16:04:50 CST 2016, time=2016-12-08, status=1, ipAttribution=)]
    2016-12-16 MyQueen

    高血压很多人都有,但是AD还是少数,

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1735468, encodeId=a76e1e3546885, content=<a href='/topic/show?id=7f019e71750' target=_blank style='color:#2F92EE;'>#阿兹海默病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97717, encryptionId=7f019e71750, topicName=阿兹海默病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ff833907849, createdName=xre2019, createdTime=Mon Feb 13 11:52:00 CST 2017, time=2017-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1982039, encodeId=976c198203902, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Sat Mar 11 20:52:00 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=163810, encodeId=870116381093, content=很好,不错,以后会多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzUn81b5CF5ibVPib8jWI92iciaxmqGHlwruOnK4SVZykd4iahqo1hicklIibyZoxm55X7EM8BW9eX1h1hQ2/0, createdBy=8aa81937526, createdName=李东泽, createdTime=Sun Dec 18 15:25:03 CST 2016, time=2016-12-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=163197, encodeId=d00916319e36, content=高血压很多人都有,但是AD还是少数,, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29ab1719082, createdName=MyQueen, createdTime=Fri Dec 16 08:37:45 CST 2016, time=2016-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=161315, encodeId=61a2161315bf, content=每天吃20克坚果能降低多种疾病风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Thu Dec 08 23:23:57 CST 2016, time=2016-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=161314, encodeId=2b0d1613146d, content=每天吃20克坚果能降低多种疾病风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Thu Dec 08 23:23:50 CST 2016, time=2016-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=161229, encodeId=6319161229c0, content=学习了很多先进的医学知识讲座, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161027/IMG58114E1818EA51495.jpg, createdBy=4b2c1959822, createdName=雅文博武, createdTime=Thu Dec 08 16:04:50 CST 2016, time=2016-12-08, status=1, ipAttribution=)]
    2016-12-08 ann y

    每天吃20克坚果能降低多种疾病风险

    0

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    2016-12-08 ann y

    每天吃20克坚果能降低多种疾病风险

    0

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    2016-12-08 雅文博武

    学习了很多先进的医学知识讲座

    0

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