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Nat Neurosc:中外合作研究揭示精神疾病发生调控机制

2018-11-09 佚名 科学网

近日,中国科学院动物研究所、美国埃默里大学医学院、中国科学院干细胞与再生医学创新研究院、中国科学院大学、美国圣裘德儿童研究医院,东南大学等机构合作,首次提供了miR-137缺失导致精神疾病的在体实验证据,进一步揭示miR-137缺失类的精神疾病的分子调控机制。

近日,中国科学院动物研究所、美国埃默里大学医学院、中国科学院干细胞与再生医学创新研究院、中国科学院大学、美国圣裘德儿童研究医院,东南大学等机构合作,首次提供了miR-137缺失导致精神疾病的在体实验证据,进一步揭示miR-137缺失类的精神疾病的分子调控机制。该研究11月5日在线发表于《自然—神经科学》。

精神疾病是一类行为、认知、学习、情感等精神活动障碍的神经疾病。目前对其病因的认识尚不明确,且缺乏有效的治疗药物。

近年来,多项独立的全基因组关联分析研究发现,染色体上MIR137基因编码区(1p21.3,编码小分子非编码RNA miR-137)突变与精神分裂症的发生密切相关。

“我们在早期的研究工作中,利用基因过表达与敲低的慢病毒与逆转录病毒等技术已经证实了miR-137在神经发生、神经元成熟、突出可塑性、学习记忆等方面行使着重要功能。”论文通讯作者、中科院动物研究所研究员陈大华告诉《中国科学报》记者,但是miR-137缺失对个体精神活动是否有影响、有何影响、怎样影响等亟待解答的科学问题尚未攻破。

经过多年的联合攻关,研究人员构建了miR-137全身敲除小鼠以及神经系统特异敲除小鼠模型。实验发现,miR-137全身敲除或神经系统特异敲除的纯合子小鼠在出生后数周内即死亡。杂合子的miR-137敲低小鼠可以存活至成年。细胞水平检测发现,miR-137部分缺失会造成小鼠突触修剪、突触可塑性、突触蛋白表达等方面表型异常。

研究还发现,杂合子的miR-137敲低小鼠表现出明显的精神障碍,如刻板重复行为、社交能力下降、社交偏好受损、学习记忆功能缺陷等。为了深入揭示这些表型背后的分子机制,研究人员综合运用蛋白质组、转录组、分子生物学、生物化学等方法,鉴定出miR-137的一个关键靶基因,Pde10a (phosphodiesterase 10a)。通过给小鼠注射Pde10a特异性抑制剂(papaverine)、或者短发夹RNA病毒(sh-Pde10a),杂合子的miR-137敲低小鼠的刻板重复行为、社交能力、学习记忆功能得到了很好的改善。

“这些发现暗示papaverine等PDE10A抑制剂有可能成为miR-137缺失类的精神疾病的潜在药物。” 中科院动物所研究员滕兆乾表示,未来团队的研究工作重点将转向利用miR-137缺失小鼠模型、人多能干细胞与类脑体等技术手段,深入揭示miR-137缺失类的精神疾病的发病机制,评估与研发干预治疗精神疾病的药物。

原始出处:Ying Cheng, Zhi-Meng Wang, Weiqi Tan, et al. Partial loss of psychiatric risk gene Mir137 in mice causes repetitive behavior and impairs sociability and learning via increased Pde10a. Nat Neurosci. 05 November 2018

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    2019-05-21 liye789132251
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    2018-11-19 1246a5a7m90暂无昵称

    快速进入临床才是最重要的啊

    0

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    2018-11-12 红色

    23

    0

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    2018-11-12 红色

    1

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  5. [GetPortalCommentsPageByObjectIdResponse(id=1883411, encodeId=5c2118834116d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue May 21 17:43:00 CST 2019, time=2019-05-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353093, encodeId=631c353093b1, content=快速进入临床才是最重要的啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=113, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=834b2485807, createdName=1246a5a7m90暂无昵称, createdTime=Mon Nov 19 23:33:07 CST 2018, time=2018-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352398, encodeId=ab09352398a3, content=23, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:55 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352397, encodeId=dd1835239e13, content=1, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:52 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352396, encodeId=b53f35239676, content=1, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:49 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352395, encodeId=e59635239565, content=123, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:45 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364415, encodeId=6d6913644157b, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Sat Nov 10 16:43:00 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1497632, encodeId=f313149e6326e, content=<a href='/topic/show?id=02599201364' target=_blank style='color:#2F92EE;'>#调控机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92013, encryptionId=02599201364, topicName=调控机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2bce9348572, createdName=villahu, createdTime=Sat Nov 10 16:43:00 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352165, encodeId=ce383521653e, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Sat Nov 10 11:26:55 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352079, encodeId=3dab3520e938, content=嗯嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Fri Nov 09 23:50:00 CST 2018, time=2018-11-09, status=1, ipAttribution=)]
    2018-11-12 红色

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  6. [GetPortalCommentsPageByObjectIdResponse(id=1883411, encodeId=5c2118834116d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue May 21 17:43:00 CST 2019, time=2019-05-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353093, encodeId=631c353093b1, content=快速进入临床才是最重要的啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=113, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=834b2485807, createdName=1246a5a7m90暂无昵称, createdTime=Mon Nov 19 23:33:07 CST 2018, time=2018-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352398, encodeId=ab09352398a3, content=23, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:55 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352397, encodeId=dd1835239e13, content=1, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:52 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352396, encodeId=b53f35239676, content=1, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:49 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352395, encodeId=e59635239565, content=123, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:45 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364415, encodeId=6d6913644157b, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Sat Nov 10 16:43:00 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1497632, encodeId=f313149e6326e, content=<a href='/topic/show?id=02599201364' target=_blank style='color:#2F92EE;'>#调控机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92013, encryptionId=02599201364, topicName=调控机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2bce9348572, createdName=villahu, createdTime=Sat Nov 10 16:43:00 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352165, encodeId=ce383521653e, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Sat Nov 10 11:26:55 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352079, encodeId=3dab3520e938, content=嗯嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Fri Nov 09 23:50:00 CST 2018, time=2018-11-09, status=1, ipAttribution=)]
    2018-11-12 红色

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    2018-11-10 lsndxfj
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  9. [GetPortalCommentsPageByObjectIdResponse(id=1883411, encodeId=5c2118834116d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue May 21 17:43:00 CST 2019, time=2019-05-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353093, encodeId=631c353093b1, content=快速进入临床才是最重要的啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=113, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=834b2485807, createdName=1246a5a7m90暂无昵称, createdTime=Mon Nov 19 23:33:07 CST 2018, time=2018-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352398, encodeId=ab09352398a3, content=23, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:55 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352397, encodeId=dd1835239e13, content=1, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:52 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352396, encodeId=b53f35239676, content=1, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:49 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352395, encodeId=e59635239565, content=123, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:45 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364415, encodeId=6d6913644157b, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Sat Nov 10 16:43:00 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1497632, encodeId=f313149e6326e, content=<a href='/topic/show?id=02599201364' target=_blank style='color:#2F92EE;'>#调控机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92013, encryptionId=02599201364, topicName=调控机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2bce9348572, createdName=villahu, createdTime=Sat Nov 10 16:43:00 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352165, encodeId=ce383521653e, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Sat Nov 10 11:26:55 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352079, encodeId=3dab3520e938, content=嗯嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Fri Nov 09 23:50:00 CST 2018, time=2018-11-09, status=1, ipAttribution=)]
    2018-11-10 红色

    学习了

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=1883411, encodeId=5c2118834116d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue May 21 17:43:00 CST 2019, time=2019-05-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353093, encodeId=631c353093b1, content=快速进入临床才是最重要的啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=113, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=834b2485807, createdName=1246a5a7m90暂无昵称, createdTime=Mon Nov 19 23:33:07 CST 2018, time=2018-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352398, encodeId=ab09352398a3, content=23, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:55 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352397, encodeId=dd1835239e13, content=1, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:52 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352396, encodeId=b53f35239676, content=1, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:49 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352395, encodeId=e59635239565, content=123, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Mon Nov 12 17:47:45 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364415, encodeId=6d6913644157b, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Sat Nov 10 16:43:00 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1497632, encodeId=f313149e6326e, content=<a href='/topic/show?id=02599201364' target=_blank style='color:#2F92EE;'>#调控机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92013, encryptionId=02599201364, topicName=调控机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2bce9348572, createdName=villahu, createdTime=Sat Nov 10 16:43:00 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352165, encodeId=ce383521653e, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Sat Nov 10 11:26:55 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352079, encodeId=3dab3520e938, content=嗯嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=080f2478288, createdName=红色, createdTime=Fri Nov 09 23:50:00 CST 2018, time=2018-11-09, status=1, ipAttribution=)]
    2018-11-09 红色

    嗯嗯

    0

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