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J Mol Cell Biol:陈剑峰研究组揭示妊娠期肝内胆汁淤积症患者胎盘炎性反应的发生机制

2017-04-27 佚名 上海生命科学研究院

近期,国际学术期刊《分子细胞生物学杂志》(Journal of Molecular Cell Biology)在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所陈剑峰研究组的最新研究成果:Bile acids evoke placental inflammation by activating Gpbar1/NF-κB pathway in intrahepatic cholesta

近期,国际学术期刊《分子细胞生物学杂志》(Journal of Molecular Cell Biology)在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所陈剑峰研究组的最新研究成果:Bile acids evoke placental inflammation by activating Gpbar1/NF-κB pathway in intrahepatic cholestasis of pregnancy。该工作发现,妊娠期肝内胆汁淤积症(Intrahepatic cholestasis of pregnancy,以下简称ICP)患者血清中高浓度的胆汁酸通过激活胎盘滋养层细胞中的Gpbar1/NF-κB信号通路引发胎盘过度炎症反应,从而对胎儿造成不良影响,在动物模型中,抑制Gpbar1/NF-κB能够显着改善胎盘炎症和胎鼠生存率。

ICP是一种妊娠期孕妇出现的以皮肤瘙痒、黄疸为主要临床表现,以血胆汁酸升高、肝酶异常为主要特征的妊娠期并发症,该病在我国的发病率达2%-4%。该病的主要危害在于对围产儿的不良影响,包括:早产(19-60%)、胎儿宫内窘迫(22-33%)、胎死宫内(1-2%)等。尽管之前的研究已经建立了母体血清中高浓度的胆汁酸与胎儿预后不良之间的相关性,但是孕妇高浓度的胆汁酸如何引起胎儿不良反应的机制未知。

在陈剑峰指导下,张有华等研究人员发现血清高浓度胆汁酸可以通过胎盘滋养层细胞表面Gpbar1受体激活NF-κB信号通路,促进VCAM-1和多种炎症因子的表达,从而引起胎盘中淋巴细胞异常浸润与胎盘炎症,进而对胎儿产生负面影响。熊去氧胆酸和穿心莲内酯可以通过抑制Gpbar1受体或NF-κB通路抑制胆汁酸诱导的胎盘炎症,极大地改善ICP大鼠模型中胎鼠生存率,并且穿心莲内酯的效果要好于现有临床药物熊去氧胆酸。该工作不但阐明了ICP中胎盘微环境胆汁酸对淋巴细胞黏附与迁移的调控机制及其在ICP中的作用机理,而且探讨了两种临床药物对ICP的治疗作用及其机制,提出穿心莲内酯可能作为更有效的ICP临床药物的可能性,对ICP的机理研究和临床治疗具有重要价值。

该项工作是由上海生科院生化与细胞所和上海市第一妇婴保健院紧密合作、共同完成的,并获得了国家自然科学基金委、国家科技部“973”计划和上海市科学技术委员会的经费支持。该成果数据收集工作得到了生化与细胞所细胞分析技术平台、分子生物学技术平台、动物实验技术平台的支持。

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createdBy=188310331118, createdName=ms6390871039024434, createdTime=Sat Apr 29 07:45:00 CST 2017, time=2017-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1579170, encodeId=e38915e9170a4, content=<a href='/topic/show?id=372b834e673' target=_blank style='color:#2F92EE;'>#胆汁#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83476, encryptionId=372b834e673, topicName=胆汁)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2a0616505872, createdName=108807375_62823132, createdTime=Sat Apr 29 07:45:00 CST 2017, time=2017-04-29, status=1, ipAttribution=)]
    2017-09-21 sunylz
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target=_blank style='color:#2F92EE;'>#胎盘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83657, encryptionId=2aca8365e2c, topicName=胎盘)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTItxfbnwF4Yku2j227me6wl2EGarBoTicR3tHxrMtib5tnyyEEsgxlHkk8JAS4ZjHsEF7PxhBwh1QwQ/132, createdBy=c8162575557, createdName=liuyong2981, createdTime=Sat Apr 29 07:45:00 CST 2017, time=2017-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511306, encodeId=4cab151130601, content=<a href='/topic/show?id=0a493e89802' target=_blank style='color:#2F92EE;'>#发生机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37898, encryptionId=0a493e89802, topicName=发生机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=188310331118, createdName=ms6390871039024434, createdTime=Sat Apr 29 07:45:00 CST 2017, time=2017-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1579170, encodeId=e38915e9170a4, content=<a href='/topic/show?id=372b834e673' target=_blank style='color:#2F92EE;'>#胆汁#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83476, encryptionId=372b834e673, topicName=胆汁)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2a0616505872, createdName=108807375_62823132, createdTime=Sat Apr 29 07:45:00 CST 2017, time=2017-04-29, status=1, ipAttribution=)]
    2017-11-01 维他命
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target=_blank style='color:#2F92EE;'>#胎盘#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83657, encryptionId=2aca8365e2c, topicName=胎盘)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTItxfbnwF4Yku2j227me6wl2EGarBoTicR3tHxrMtib5tnyyEEsgxlHkk8JAS4ZjHsEF7PxhBwh1QwQ/132, createdBy=c8162575557, createdName=liuyong2981, createdTime=Sat Apr 29 07:45:00 CST 2017, time=2017-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511306, encodeId=4cab151130601, content=<a href='/topic/show?id=0a493e89802' target=_blank style='color:#2F92EE;'>#发生机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37898, encryptionId=0a493e89802, topicName=发生机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=188310331118, createdName=ms6390871039024434, createdTime=Sat Apr 29 07:45:00 CST 2017, time=2017-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1579170, encodeId=e38915e9170a4, content=<a href='/topic/show?id=372b834e673' target=_blank style='color:#2F92EE;'>#胆汁#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83476, encryptionId=372b834e673, topicName=胆汁)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2a0616505872, createdName=108807375_62823132, createdTime=Sat Apr 29 07:45:00 CST 2017, time=2017-04-29, status=1, ipAttribution=)]
    2017-05-03 东宝

    是不是意味着有别的选择来降胆酸,改善预后了

    0

  7. 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