Circulation:糖尿病患者血小板表达活化的P2Y12受体

2017-06-24 xiangting MedSci原创

血小板P2Y12受体表达显著增加,在T2DM患者中该受体被结构性激活,这导致血小板机能亢进并限制了T2DM中抗血小板药物的疗效。

糖尿病患者的血小板是极度活跃的。过活化的血小板可能导致心血管并发症和对抗血小板药物的反应不良。然而,过活化血小板的潜在机制尚不完全清楚。

研究人员测量了2型糖尿病(T2DM)患者和糖尿病大鼠血小板上的P2Y12表达。还通过测量cAMP和VASP磷酸化测定血小板P2Y12活化。比较了大鼠AR-C78511和坎格雷洛的抗血小板和抗血栓形成作用。最后还探索了在巨核细胞中调节P2Y12受体表达的NFκB通路的作用。

2型糖尿病患者血小板P2Y12水平是健康人的4倍。P2Y12表达与ADP诱导的血小板聚集相关(r = 0.89, P <0.01)。糖尿病患者血小板的P2Y12被结构性激活。尽管AR-C78511(一种有效的P2Y12反向激动剂)和坎格雷洛对健康人的血小板具有相似的抗血小板功效,但是对于糖尿病血小板而言,AR-C78511的抗血小板作用更强(聚集率为36±3%vs 49±5% , P <0.05)。在大鼠中使用FeCl3损伤的肠系膜动脉血栓模型和大鼠AV分流血栓模型,发现反向激动剂AR-C78511对糖尿病GK大鼠的抗血栓作用比坎格雷洛更强(血栓重量为4.9±0.3mg vs.8.3±0.4mg, P <0.01)。此外还发现,涉及高血糖-ROS-NFκB途径增加糖尿病血小板P2Y12受体表达。

血小板P2Y12受体表达显著增加,在T2DM患者中该受体被结构性激活,这导致血小板机能亢进并限制了T2DM中抗血小板药物的疗效。

原始出处:
Liang Hu, Lin Chang, Yan Zhang,et al. Platelets Express Activated P2Y12 Receptor in Patients with Diabetes. Circulation. 21 June 2017.

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  1. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3e502075746, createdName=营养医师, createdTime=Sun Jun 25 14:00:55 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215235, encodeId=780e21523587, content=学习了 复习了这个通路的作用, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7SEMbIqicph9XjjB508YwgovWXrJrvXs6oQCG2x4iaUOS1ouvNLf8dRtkwfFsMN1sRUP5e5rbr7eUJPS8Gdt0aOq/0, createdBy=99cf2073595, createdName=蒋宇, createdTime=Sun Jun 25 13:53:22 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215224, encodeId=aed321522438, content=糖尿病越来越多并发症, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 25 13:27:45 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215161, encodeId=574121516111, content=不错的,学习了,谢谢分享!, 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/mStl88fu4NdqKgfW3nMpOkC3jXxiaW2po0PtglY5ZuVjERqKADW4HyMI8bcZXWlKgH7tEP9ULBoBzuQMibia4pr1s9rQPqLvqQJ/0, createdBy=e8c02060444, createdName=中医痴, createdTime=Sun Jun 25 10:08:15 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=214994, encodeId=c253214994bf, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, 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    2017-09-03 yeye5224612
  2. 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createdName=虈亣靌, createdTime=Tue Jun 27 14:14:29 CST 2017, time=2017-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1474223, encodeId=334e14e422328, content=<a href='/topic/show?id=935fe6718e3' target=_blank style='color:#2F92EE;'>#糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76718, encryptionId=935fe6718e3, topicName=糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a38f7243741, createdName=xue8604, createdTime=Mon Jun 26 08:21:00 CST 2017, time=2017-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215368, encodeId=7c4c215368a5, content=感谢分享!继续关注!, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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    2017-06-27 虈亣靌

    很值得期待,据说很好

    0

  3. 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  4. 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createdName=虈亣靌, createdTime=Tue Jun 27 14:14:29 CST 2017, time=2017-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1474223, encodeId=334e14e422328, content=<a href='/topic/show?id=935fe6718e3' target=_blank style='color:#2F92EE;'>#糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76718, encryptionId=935fe6718e3, topicName=糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a38f7243741, createdName=xue8604, createdTime=Mon Jun 26 08:21:00 CST 2017, time=2017-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215368, encodeId=7c4c215368a5, content=感谢分享!继续关注!, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好!, createdTime=Sun Jun 25 22:31:43 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215288, encodeId=5b3c215288dc, content=血小板P2Y12受体表达显著增加,在T2DM患者中该受体被结构性激活,这导致血小板机能亢进并限制了T2DM中抗血小板药物的疗效。, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Sun Jun 25 16:39:12 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215237, encodeId=178321523e9a, content=牛逼啊。中国人发这么高的杂志, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3e502075746, createdName=营养医师, createdTime=Sun Jun 25 14:00:55 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215235, encodeId=780e21523587, content=学习了 复习了这个通路的作用, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7SEMbIqicph9XjjB508YwgovWXrJrvXs6oQCG2x4iaUOS1ouvNLf8dRtkwfFsMN1sRUP5e5rbr7eUJPS8Gdt0aOq/0, createdBy=99cf2073595, createdName=蒋宇, createdTime=Sun Jun 25 13:53:22 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215224, encodeId=aed321522438, content=糖尿病越来越多并发症, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 25 13:27:45 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215161, encodeId=574121516111, content=不错的,学习了,谢谢分享!, 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/mStl88fu4NdqKgfW3nMpOkC3jXxiaW2po0PtglY5ZuVjERqKADW4HyMI8bcZXWlKgH7tEP9ULBoBzuQMibia4pr1s9rQPqLvqQJ/0, createdBy=e8c02060444, createdName=中医痴, createdTime=Sun Jun 25 10:08:15 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=214994, encodeId=c253214994bf, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sun Jun 25 00:39:03 CST 2017, time=2017-06-25, status=1, ipAttribution=)]
    2017-06-25 明天会更好!

    感谢分享!继续关注!

    0

  5. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 25 13:27:45 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215161, encodeId=574121516111, content=不错的,学习了,谢谢分享!, 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/mStl88fu4NdqKgfW3nMpOkC3jXxiaW2po0PtglY5ZuVjERqKADW4HyMI8bcZXWlKgH7tEP9ULBoBzuQMibia4pr1s9rQPqLvqQJ/0, createdBy=e8c02060444, createdName=中医痴, createdTime=Sun Jun 25 10:08:15 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=214994, encodeId=c253214994bf, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sun Jun 25 00:39:03 CST 2017, time=2017-06-25, status=1, ipAttribution=)]
    2017-06-25 有备才能无患

    血小板P2Y12受体表达显著增加,在T2DM患者中该受体被结构性激活,这导致血小板机能亢进并限制了T2DM中抗血小板药物的疗效。

    0

  6. 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createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好!, createdTime=Sun Jun 25 22:31:43 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215288, encodeId=5b3c215288dc, content=血小板P2Y12受体表达显著增加,在T2DM患者中该受体被结构性激活,这导致血小板机能亢进并限制了T2DM中抗血小板药物的疗效。, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Sun Jun 25 16:39:12 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215237, encodeId=178321523e9a, content=牛逼啊。中国人发这么高的杂志, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 25 13:27:45 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215161, encodeId=574121516111, content=不错的,学习了,谢谢分享!, 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/mStl88fu4NdqKgfW3nMpOkC3jXxiaW2po0PtglY5ZuVjERqKADW4HyMI8bcZXWlKgH7tEP9ULBoBzuQMibia4pr1s9rQPqLvqQJ/0, createdBy=e8c02060444, createdName=中医痴, createdTime=Sun Jun 25 10:08:15 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=214994, encodeId=c253214994bf, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sun Jun 25 00:39:03 CST 2017, time=2017-06-25, status=1, ipAttribution=)]
    2017-06-25 营养医师

    牛逼啊。中国人发这么高的杂志

    0

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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 25 13:27:45 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215161, encodeId=574121516111, content=不错的,学习了,谢谢分享!, 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/mStl88fu4NdqKgfW3nMpOkC3jXxiaW2po0PtglY5ZuVjERqKADW4HyMI8bcZXWlKgH7tEP9ULBoBzuQMibia4pr1s9rQPqLvqQJ/0, createdBy=e8c02060444, createdName=中医痴, createdTime=Sun Jun 25 10:08:15 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=214994, encodeId=c253214994bf, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sun Jun 25 00:39:03 CST 2017, time=2017-06-25, status=1, ipAttribution=)]
    2017-06-25 蒋宇

    学习了 复习了这个通路的作用

    0

  8. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 25 13:27:45 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215161, encodeId=574121516111, content=不错的,学习了,谢谢分享!, 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/mStl88fu4NdqKgfW3nMpOkC3jXxiaW2po0PtglY5ZuVjERqKADW4HyMI8bcZXWlKgH7tEP9ULBoBzuQMibia4pr1s9rQPqLvqQJ/0, createdBy=e8c02060444, createdName=中医痴, createdTime=Sun Jun 25 10:08:15 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=214994, encodeId=c253214994bf, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sun Jun 25 00:39:03 CST 2017, time=2017-06-25, status=1, ipAttribution=)]
    2017-06-25 flysky120

    糖尿病越来越多并发症

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1940206, encodeId=214319402068c, content=<a href='/topic/show?id=18f81361276' target=_blank style='color:#2F92EE;'>#P2Y12#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13612, encryptionId=18f81361276, topicName=P2Y12)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=yeye5224612, createdTime=Sun Sep 03 04:21:00 CST 2017, time=2017-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215993, encodeId=5bc52159936f, content=很值得期待,据说很好, 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, 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 25 13:27:45 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215161, encodeId=574121516111, content=不错的,学习了,谢谢分享!, 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/mStl88fu4NdqKgfW3nMpOkC3jXxiaW2po0PtglY5ZuVjERqKADW4HyMI8bcZXWlKgH7tEP9ULBoBzuQMibia4pr1s9rQPqLvqQJ/0, createdBy=e8c02060444, createdName=中医痴, createdTime=Sun Jun 25 10:08:15 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=214994, encodeId=c253214994bf, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sun Jun 25 00:39:03 CST 2017, time=2017-06-25, status=1, ipAttribution=)]
    2017-06-25 中医痴

    不错的,学习了,谢谢分享!

    0

  10. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Sun Jun 25 13:27:45 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=215161, encodeId=574121516111, content=不错的,学习了,谢谢分享!, 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/mStl88fu4NdqKgfW3nMpOkC3jXxiaW2po0PtglY5ZuVjERqKADW4HyMI8bcZXWlKgH7tEP9ULBoBzuQMibia4pr1s9rQPqLvqQJ/0, createdBy=e8c02060444, createdName=中医痴, createdTime=Sun Jun 25 10:08:15 CST 2017, time=2017-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=214994, encodeId=c253214994bf, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sun Jun 25 00:39:03 CST 2017, time=2017-06-25, status=1, ipAttribution=)]
    2017-06-25 130****4638

    学习了谢谢分享

    0

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