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Hepatology：11-羟类固醇脱氢酶1缺乏或被抑制，可增强小鼠肌成纤维细胞的激活能力

2018-06-26 MedSci MedSci原创

11Beta-hydroxysteroiddehydrogenase-1缺乏抑制肝纤维化小鼠
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11β-HSD1缺乏能够增强肌成纤维细胞的活化能力，促进化学肝损伤后的初始纤维化；因此，11β-HSD1抑制剂对肝脏损伤和修复的影响可能与环境有关，值得仔细研究。

研究背景：慢性肝损伤的一个特征是纤维化，激活的肝星状细胞(HSCs)在肝纤维化中发挥着重要的作用。在体外，糖皮质激素可限制HSC的激活，经11β-羟类固醇脱氢酶-1(11betaHSD1)作用后，组织糖皮质激素水平升高。虽然在不同的小鼠模型中已经开发出11β-HSD1抑制剂用于治疗2型糖尿病和改善饮食诱导的脂肪肝，但对肝损伤的进展和/或解除以及随后的肝纤维化的影响，目前尚不清楚。

研究方法和结果：研究使用了可逆性的CCL4模型，表明在两种基因11β-HSD1缺乏（Hsd11b1(-/-)和肌成纤维细胞特异性的Hsd11b1(fl/fl) /Pdgfrb-cre，）时，11β-HSD1抑制剂能够加速肝成纤维细胞的激活和肝纤维化程度。相比之下，肝细胞特异性Hsd11b1(fl/fl) /白蛋白-cre小鼠的肝损伤和肝纤维化程度与对照组没有差异，排除了肝细胞中11betaHSD1缺乏是肝纤维化增加的原因。在原代HSC培养中，糖皮质激素抑制了关键的纤维化基因Acta2和Col1alpha1的表达，这种抑制作用被11betaHSD1抑制剂[4-(2-氯苯基4-氟-1-哌啶基)[5-(1h -吡唑啉-4-基)-3-噻吩基]-甲基苯胺所缓解。Hsd11b1(-/-)和Hsd11b1(fl/fl) /Pdgfrb-cre小鼠的HSCs表达了更高水平的Acta2和Col1alpha1，并相应地被更有效地激活。在化学药物导致肝损伤之前给予Hsd11b1(-/-)小鼠4-(2-氯苯基4-氟-1-哌啶基)[5-(1h -吡唑啉-4-基)-3-噻吩基-甲基苯胺，肝纤维化程度增加。

研究结论：11β-HSD1缺乏能够增强肌成纤维细胞的活化能力，促进化学肝损伤后的初始纤维化；因此，11β-HSD1抑制剂对肝脏损伤和修复的影响可能与环境有关，值得仔细研究。

原始出处：

Zou X， Ramachandran P， Kendall TJ， et al. 11Beta-hydroxysteroid dehydrogenase-1 deficiency or inhibition enhances hepatic myofibroblast activation in murine liver fibrosis. Hepatology， 2018， 67(6)， 2167-2181.

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    2018-06-29 ms5822920152752585

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    #EPA#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2037292, encodeId=887c203e29263, content=<a href='/topic/show?id=933f80922f5' target=_blank style='color:#2F92EE;'>#肌成纤维细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80922, encryptionId=933f80922f5, topicName=肌成纤维细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/4v5DMqK7WnzoBdibNsryQ8OEM5gFSdRH9j3HNCKPfKXlObInweOSHdQPATeTicYp7nvg3bsgicjLgRkdlhrpry21w/132, createdBy=6bf82500013, createdName=ms5822920152752585, createdTime=Fri Jun 29 19:11:00 CST 2018, time=2018-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1307092, encodeId=2653130e09204, content=<a href='/topic/show?id=6dab540565f' target=_blank style='color:#2F92EE;'>#成纤维细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54056, encryptionId=6dab540565f, topicName=成纤维细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Thu Jun 28 13:11:00 CST 2018, time=2018-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1313395, encodeId=4e7f131339569, content=<a href='/topic/show?id=d59be61251d' target=_blank style='color:#2F92EE;'>#类固醇#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76125, encryptionId=d59be61251d, topicName=类固醇)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a691420, createdName=30397604, createdTime=Thu Jun 28 13:11:00 CST 2018, time=2018-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1427148, encodeId=f764142e14882, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Thu Jun 28 13:11:00 CST 2018, time=2018-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1462775, encodeId=8bdf1462e75ff, content=<a href='/topic/show?id=fbbce726228' target=_blank style='color:#2F92EE;'>#纤维细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77262, encryptionId=fbbce726228, topicName=纤维细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c516518840, createdName=marongnuan, createdTime=Thu Jun 28 13:11:00 CST 2018, time=2018-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=327239, encodeId=fc5032e23934, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Tue Jun 26 22:24:02 CST 2018, time=2018-06-26, status=1, ipAttribution=)]
    2018-06-28 marongnuan

    #纤维细胞#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2037292, encodeId=887c203e29263, content=<a href='/topic/show?id=933f80922f5' target=_blank style='color:#2F92EE;'>#肌成纤维细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80922, encryptionId=933f80922f5, topicName=肌成纤维细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/4v5DMqK7WnzoBdibNsryQ8OEM5gFSdRH9j3HNCKPfKXlObInweOSHdQPATeTicYp7nvg3bsgicjLgRkdlhrpry21w/132, createdBy=6bf82500013, createdName=ms5822920152752585, createdTime=Fri Jun 29 19:11:00 CST 2018, time=2018-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1307092, encodeId=2653130e09204, content=<a href='/topic/show?id=6dab540565f' target=_blank style='color:#2F92EE;'>#成纤维细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54056, encryptionId=6dab540565f, topicName=成纤维细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Thu Jun 28 13:11:00 CST 2018, time=2018-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1313395, encodeId=4e7f131339569, content=<a href='/topic/show?id=d59be61251d' target=_blank style='color:#2F92EE;'>#类固醇#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76125, encryptionId=d59be61251d, topicName=类固醇)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a691420, createdName=30397604, createdTime=Thu Jun 28 13:11:00 CST 2018, time=2018-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1427148, encodeId=f764142e14882, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Thu Jun 28 13:11:00 CST 2018, time=2018-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1462775, encodeId=8bdf1462e75ff, content=<a href='/topic/show?id=fbbce726228' target=_blank style='color:#2F92EE;'>#纤维细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77262, encryptionId=fbbce726228, topicName=纤维细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c516518840, createdName=marongnuan, createdTime=Thu Jun 28 13:11:00 CST 2018, time=2018-06-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=327239, encodeId=fc5032e23934, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Tue Jun 26 22:24:02 CST 2018, time=2018-06-26, status=1, ipAttribution=)]
    2018-06-26 wqkm

    ^_^^_^^_^

    0