Hepatology:灯盏花素减轻非酒精性脂肪性肝炎的机制研究

2021-10-31 Vivi MedSci原创

灯盏花素通过直接抑制TAK1信号传导来阻止代谢应激诱导的NASH进展,可能是治疗NASH的一种新的候选药物。

非酒精性脂肪性肝病(NAFLD)是从非酒精性脂肪性肝(NAFL)非酒精性脂肪性肝炎(NASH)等代谢综合征的重要环节,目前正成为全球范围内肝硬化和肝癌的主要病因。然而,由于NASH的病理生理机制复杂且不明确,目前还没有得到批准的治疗NASH的特异性药物

灯盏花素是一种从传统中药灯盏花中分离出来的天然类黄酮处方药,具有广泛的药理作用,包括对代谢的影响。然而,灯盏花素的抗NASH疗效及作用机制尚未明确。

近期在肝脏病学杂志Hepatology发表的一项研究,利用体内和体外实验,通过组织病理观察、血清生化检测(TG、TC)、蛋白免疫印迹实验(成脂基因FASN和PPARγ)、RNA测序、蛋白组学分析等,评估了灯盏花素在代谢应激下对肝脏脂肪变性、炎症和纤维化发展的影响。

结果显示,灯盏花素治疗显著减少高脂饮食(HFD)、高脂/高胆固醇饮食(HFHC)或蛋氨酸和胆碱缺乏饮食(MCD)小鼠的脂质堆积、炎症细胞浸润、肝损伤和纤维化。此外,灯盏花素还能减轻代谢应激肝细胞的脂质积累、炎症和脂毒性。RNA测序和多组学分析进一步表明灯盏花素抗NASH作用的关键机制是抑制TAK1磷酸化和随后的MAPK信号级联。用TAK1的选择性抑制剂5Z-7-oxozeaenol处理可消除代谢应激下灯盏花素介导的肝保护作用。分子对接表明灯盏花素直接与TAK1结合。

这些结果表明,灯盏花素通过直接抑制TAK1信号传导来阻止代谢应激诱导的NASH进展。灯盏花素可能是治疗NASH的一种新的候选药物。

 

文献来源:

Lan, T., Jiang, S., Zhang, J., Weng, Q., Yu, Y., Li, H., Tian, S., Ding, X., Hu, S., Yang, Y., Wang, W., Wang, L., Luo, D., Xiao, X., Piao, S., Zhu, Q., Rong, X., & Guo, J. (2021). Breviscapine Alleviates Nonalcoholic Steatohepatitis by Inhibiting TGF-β-activated Kinase 1-dependent Signaling. Hepatology (Baltimore, Md.), 10.1002/hep.32221. Advance online publication. https://doi.org/10.1002/hep.32221

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    2022-02-21 qjddjq
  4. [GetPortalCommentsPageByObjectIdResponse(id=1956120, encodeId=d7941956120fd, content=<a href='/topic/show?id=8a048435058' target=_blank style='color:#2F92EE;'>#脂肪性肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84350, encryptionId=8a048435058, topicName=脂肪性肝炎)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Jr8S1dfvNyP22t32IFDXJXnpd5AGlDibiajL5cl3pxj7OPCeAeibLhzOmZn5Q2Oicc6uKOCnxGNOggdLtI3hIW7huQ/132, createdBy=66e52500008, createdName=Tamikia, createdTime=Sat Feb 12 20:56:44 CST 2022, time=2022-02-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676669, encodeId=4d1a16e66695b, content=<a href='/topic/show?id=397299e19c7' target=_blank style='color:#2F92EE;'>#非酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99719, encryptionId=397299e19c7, topicName=非酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d18c27357544, createdName=Tommy1958, createdTime=Wed Jan 05 07:56:44 CST 2022, time=2022-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1810218, encodeId=8b631810218f3, content=<a href='/topic/show?id=70f484349b5' target=_blank style='color:#2F92EE;'>#脂肪性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84349, encryptionId=70f484349b5, topicName=脂肪性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Mon Feb 21 09:56:44 CST 2022, time=2022-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1673698, encodeId=035316e3698f3, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=398f26933958, createdName=huiwelcome, createdTime=Tue May 03 14:56:44 CST 2022, time=2022-05-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2056223, encodeId=2356205622316, content=<a href='/topic/show?id=616b611e9bc' target=_blank style='color:#2F92EE;'>#机制研究#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61179, encryptionId=616b611e9bc, topicName=机制研究)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri May 20 04:56:44 CST 2022, time=2022-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1081432, encodeId=170f108143290, content=这很中西医结合,关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210127/50a003c4097845e182c08afd64d8a509/bd766dfebe9c40e0bca2dae964601bdc.jpg, createdBy=22de5454917, createdName=carrotlyl, createdTime=Sat Dec 18 07:26:50 CST 2021, time=2021-12-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067603, encodeId=ef12106e6032f, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=801b5560292, createdName=杨致, createdTime=Sat Nov 06 15:45:57 CST 2021, time=2021-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066451, encodeId=7f9e1066451f2, content=学习了,非常感谢🙏, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2020/02/15/7274ed1be4747d648e4e2f7f62fae403.jpg, createdBy=d8d65273314, createdName=1482963am12暂无昵称, createdTime=Wed Nov 03 00:56:20 CST 2021, time=2021-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1427569, encodeId=fe56142e56982, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, 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=Tue Nov 02 13:56:44 CST 2021, time=2021-11-02, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1956120, encodeId=d7941956120fd, content=<a href='/topic/show?id=8a048435058' target=_blank style='color:#2F92EE;'>#脂肪性肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84350, encryptionId=8a048435058, topicName=脂肪性肝炎)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Jr8S1dfvNyP22t32IFDXJXnpd5AGlDibiajL5cl3pxj7OPCeAeibLhzOmZn5Q2Oicc6uKOCnxGNOggdLtI3hIW7huQ/132, createdBy=66e52500008, createdName=Tamikia, createdTime=Sat Feb 12 20:56:44 CST 2022, time=2022-02-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676669, encodeId=4d1a16e66695b, content=<a href='/topic/show?id=397299e19c7' target=_blank style='color:#2F92EE;'>#非酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99719, encryptionId=397299e19c7, topicName=非酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d18c27357544, createdName=Tommy1958, createdTime=Wed Jan 05 07:56:44 CST 2022, time=2022-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1810218, encodeId=8b631810218f3, content=<a href='/topic/show?id=70f484349b5' target=_blank style='color:#2F92EE;'>#脂肪性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84349, encryptionId=70f484349b5, topicName=脂肪性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Mon Feb 21 09:56:44 CST 2022, time=2022-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1673698, encodeId=035316e3698f3, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=398f26933958, createdName=huiwelcome, createdTime=Tue May 03 14:56:44 CST 2022, time=2022-05-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2056223, encodeId=2356205622316, content=<a href='/topic/show?id=616b611e9bc' target=_blank style='color:#2F92EE;'>#机制研究#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61179, encryptionId=616b611e9bc, topicName=机制研究)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri May 20 04:56:44 CST 2022, time=2022-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1081432, encodeId=170f108143290, content=这很中西医结合,关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210127/50a003c4097845e182c08afd64d8a509/bd766dfebe9c40e0bca2dae964601bdc.jpg, createdBy=22de5454917, createdName=carrotlyl, createdTime=Sat Dec 18 07:26:50 CST 2021, time=2021-12-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067603, encodeId=ef12106e6032f, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=801b5560292, createdName=杨致, createdTime=Sat Nov 06 15:45:57 CST 2021, time=2021-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1066451, encodeId=7f9e1066451f2, content=学习了,非常感谢🙏, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2020/02/15/7274ed1be4747d648e4e2f7f62fae403.jpg, createdBy=d8d65273314, createdName=1482963am12暂无昵称, createdTime=Wed Nov 03 00:56:20 CST 2021, time=2021-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1427569, encodeId=fe56142e56982, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, 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=Tue Nov 02 13:56:44 CST 2021, time=2021-11-02, status=1, ipAttribution=)]
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    2021-12-18 carrotlyl

    这很中西医结合,关注

    0

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    2021-11-06 杨致

    谢谢分享

    0

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    2021-11-03 1482963am12暂无昵称

    学习了,非常感谢🙏

    0

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    2021-11-02 gwc384

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