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Circ Res：生长激素释放激素及其激动剂对血管钙化的调节作用

2018-04-11 MedSci MedSci原创

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血管钙化（VC）是动脉粥样硬化疾病严重程度的标志。激素在调节钙化中发挥重要作用，雌激素和副甲状腺激素发挥相反作用，前者缓解VC，后者则加剧。到目前为止，尚未制定任何治疗策略来调节临床VC。本研究旨在探讨生长激素释放激素（GHRH）及其激动剂（GHRH-A）对小鼠VC模型的阻断作用。使用年轻成人骨保护素缺乏（OPG-/-）小鼠每天皮下注射GHRH-A（MR409）4周。结果显示，MR409治疗小鼠主

血管钙化（VC）是动脉粥样硬化疾病严重程度的标志。激素在调节钙化中发挥重要作用，雌激素和副甲状腺激素发挥相反作用，前者缓解VC，后者则加剧。到目前为止，尚未制定任何治疗策略来调节临床VC。本研究旨在探讨生长激素释放激素（GHRH）及其激动剂（GHRH-A）对小鼠VC模型的阻断作用。

使用年轻成人骨保护素缺乏（OPG-/-）小鼠每天皮下注射GHRH-A（MR409）4周。结果显示，MR409治疗小鼠主动脉钙化明显降低，碱性磷酸酶（ALP）活性明显降低，包括成骨标志物基因Runx2及其下游因子骨粘连蛋白和骨钙蛋白的转录因子表达也明显降低。

使用人和小鼠主动脉分离的平滑肌细胞（SMCs）探究GHRH-A的作用机制。GHRH或MR409的存在抑制成骨培养基（OM）诱导的SMCs的钙化， ALP活性和Runx2表达降低证实了此点。MR409抑制钙化被MIA602或GHRH受体选择性siRNA（GHRH拮抗剂）部分逆转。使用MR409处理诱导升高的胞质cAMP及其靶标、蛋白激酶A（PKA），继而阻断NADPH氧化酶活性并减少活性氧（ROS）的产生，从而阻断NFκB（p65）的磷酸化，此为RANKL-Runx2/ALP成骨的关键中间体。PKA选择性siRNA或化学抑制剂H89消除了MR409的这些有益作用。

该研究结果表明，SMCs中GHRH-A通过靶向PKA和NFκB（p65）之间的串扰，并通过抑制诱导Runx2基因和ALP抑制ROS产生来控制成骨。由此阻断炎症介导的骨生成。GHRH-A或是一种调节VC的新的治疗策略。

原始出处：

Shen J, Zhang N, et al., Regulation of Vascular Calcification by Growth Hormone-Releasing Hormone and its Agonists. Circ Res. 2018 Apr 4. pii: CIRCRESAHA.117.312418. doi: 10.1161/CIRCRESAHA.117.312418. 

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authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Apr 12 00:20:20 CST 2018, time=2018-04-12, status=1, ipAttribution=)]
    2018-04-15 Y—xianghai

    学习了新知识

    0

  5. 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authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Apr 12 00:20:20 CST 2018, time=2018-04-12, status=1, ipAttribution=)]
    2018-04-15 Y—xianghai

    学习了新知识

    0

  6. 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authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Apr 12 00:20:20 CST 2018, time=2018-04-12, status=1, ipAttribution=)]
    2018-04-15 Y—xianghai

    学习了新知识

    0

  7. 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topicName=激动剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=95bc21134754, createdName=medscijoin, createdTime=Fri Apr 13 06:59:00 CST 2018, time=2018-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305098, encodeId=7b3b30509823, content=学习了.长知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Thu Apr 12 13:27:34 CST 2018, time=2018-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304936, encodeId=1b8f304936be, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, 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    2018-04-15 Y—xianghai

    学习了新知识

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=305937, encodeId=07b030593e1e, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:52 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305936, encodeId=32053059367d, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:45 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305935, encodeId=201030593586, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:39 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305934, encodeId=c5ca305934fc, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:33 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305933, encodeId=107d30593365, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:28 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305932, encodeId=add53059324f, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:22 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305931, encodeId=ec2c30593142, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:16 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1627762, encodeId=12d5162e76275, content=<a href='/topic/show?id=ab4f66e8913' target=_blank style='color:#2F92EE;'>#激动剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66789, encryptionId=ab4f66e8913, topicName=激动剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=95bc21134754, createdName=medscijoin, createdTime=Fri Apr 13 06:59:00 CST 2018, time=2018-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305098, encodeId=7b3b30509823, content=学习了.长知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Thu Apr 12 13:27:34 CST 2018, time=2018-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304936, encodeId=1b8f304936be, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Apr 12 00:20:20 CST 2018, time=2018-04-12, status=1, ipAttribution=)]
    2018-04-13 medscijoin

    #激动剂#

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=305937, encodeId=07b030593e1e, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:52 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305936, encodeId=32053059367d, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:45 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305935, encodeId=201030593586, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:39 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305934, encodeId=c5ca305934fc, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:33 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305933, encodeId=107d30593365, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:28 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305932, encodeId=add53059324f, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:22 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305931, encodeId=ec2c30593142, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:16 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1627762, encodeId=12d5162e76275, content=<a href='/topic/show?id=ab4f66e8913' target=_blank style='color:#2F92EE;'>#激动剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66789, encryptionId=ab4f66e8913, topicName=激动剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=95bc21134754, createdName=medscijoin, createdTime=Fri Apr 13 06:59:00 CST 2018, time=2018-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305098, encodeId=7b3b30509823, content=学习了.长知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Thu Apr 12 13:27:34 CST 2018, time=2018-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304936, encodeId=1b8f304936be, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Apr 12 00:20:20 CST 2018, time=2018-04-12, status=1, ipAttribution=)]
    2018-04-12 1ddf0692m34(暂无匿称)

    学习了.长知识

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=305937, encodeId=07b030593e1e, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:52 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305936, encodeId=32053059367d, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:45 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305935, encodeId=201030593586, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:39 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305934, encodeId=c5ca305934fc, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:33 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305933, encodeId=107d30593365, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:28 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305932, encodeId=add53059324f, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:22 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305931, encodeId=ec2c30593142, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sun Apr 15 07:50:16 CST 2018, time=2018-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1627762, encodeId=12d5162e76275, content=<a href='/topic/show?id=ab4f66e8913' target=_blank style='color:#2F92EE;'>#激动剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66789, encryptionId=ab4f66e8913, topicName=激动剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=95bc21134754, createdName=medscijoin, createdTime=Fri Apr 13 06:59:00 CST 2018, time=2018-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=305098, encodeId=7b3b30509823, content=学习了.长知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Thu Apr 12 13:27:34 CST 2018, time=2018-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304936, encodeId=1b8f304936be, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Apr 12 00:20:20 CST 2018, time=2018-04-12, status=1, ipAttribution=)]
    2018-04-12 1209e435m98(暂无昵称)

    学习了.谢谢分享

    0

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