Hepatology:靶向治疗线粒体丙酮酸载体减轻小鼠非酒精性脂肪肝

2017-04-04 MedSci MedSci原创

肝脏相关的代谢综合征业已成为最常见但却治疗不足的肝脏疾病。非酒精性脂肪肝源于脂类在肝脏的异常沉积,然而其导致肝细胞功能紊乱、死亡以及肝纤维化的机制尚不清除。胰岛素增敏剂噻唑烷二酮类药物在治疗非酒精性脂肪肝上有效,但其广泛应用受限于其剂量限制的副作用,当前认为该副作用与氧化物酶体增殖物激活受体γ激活有关。该研究旨在确定显着减弱了激活氧化物酶体增殖物受体γ激活能力的新一代噻唑烷二酮类药物在啮齿动物非酒

肝脏相关的代谢综合征业已成为最常见但却治疗不足的肝脏疾病。非酒精性脂肪肝源于脂类在肝脏的异常沉积,然而其导致肝细胞功能紊乱、死亡以及肝纤维化的机制尚不清除。

胰岛素增敏剂噻唑烷二酮类药物在治疗非酒精性脂肪肝上有效,但其广泛应用受限于其剂量限制的副作用,当前认为该副作用与氧化物酶体增殖物激活受体γ激活有关。该研究旨在确定显着减弱了激活氧化物酶体增殖物受体γ激活能力的新一代噻唑烷二酮类药物在啮齿动物非酒精性肝硬化模型中是否可保持其有效性,同时研究其部分或全部的有益作用是否通过抑制线粒体丙酮酸载体2(MPC2)介导。最新研究发现MPC2是包括MSDC-0602在内的噻唑烷二酮类药物的线粒体结合位点。研究发现在富反式脂肪酸、果糖、胆固醇饲养的小鼠肝脏中,MSDC-0602预防和逆转肝脏纤维化,抑制星状细胞激活标志分子的表达。此外,肝脏特异性敲除MPC2的小鼠在上述饲养情况下不发生非酒精性脂肪肝。最后,MSDC-0602在体外直接减少肝星状细胞激活,MSDC-0602治疗或MPC2敲除也可间接通过影响肝脏细胞外泌体的分泌限制肝星状细胞激活。

结论:数据证明MSDC-0602在啮齿动物模型中可减弱非酒精性脂肪肝,说明针对肝脏MPC2发展靶向药物可能是一有效策略。

原文出处:

Kyle S. McCommis,Wesley T. Hodges,Elizabeth M. Brunt,et al. Targeting the mitochondrial pyruvate carrier attenuates fibrosis in a mouse model of nonalcoholic steatohepatitis. Hepatology,30 March 2017.DOI: 10.1002/hep.29025.

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content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Wed Apr 05 01:19:43 CST 2017, time=2017-04-05, status=1, ipAttribution=)]
    2017-07-27 qiaoyingli

    榜样的力量,学习的榜样。

    0

  5. 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    2017-07-16 mei539
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    2017-05-02 laoli

    谢谢分享,学习了!

    0

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content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Wed Apr 05 01:19:43 CST 2017, time=2017-04-05, status=1, ipAttribution=)]
    2017-04-13 大爰

    学习了增加见识了!

    0

  8. 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content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Wed Apr 05 01:19:43 CST 2017, time=2017-04-05, status=1, ipAttribution=)]
    2017-04-06 gwc384
  9. 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    2017-04-06 cqykthl

    脂肪肝的发病率增高趋势

    0

  10. 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    2017-04-05 飛歌

    学习了很有用

    0