Front Pharmacol:龙藤汤通过调节2型固有淋巴细胞促进胶原诱导关节炎小鼠滑膜炎症的消退

2022-03-30 紫菀款冬 MedSci原创

探究龙藤汤是否能通过调节ILC2的免疫应答机制促进类风湿关节炎滑膜炎症的消退。

背景:类风湿关节炎(RA)的病因和发病机制尚未完全阐明,传统治疗类风湿关节炎的药物不良反应较大。因此,研发中药方剂作为RA治疗的补充和替代药物尤为必要。

中药复方龙藤汤(LTD) 是北京中医药大学东直门医院治疗类风湿性关节炎的经验方,已广泛应用于临床。组成:穿山龙50 g,青风藤25 g,忍冬藤30 g,络石藤30 g,青蒿25 g,白芍25 g。伏邪痹阻是RA的核心病机,龙藤汤方中采用了大量藤类药物,取其通经走络之性,荡涤内藏邪气从血脉、经络而出,治痹于本。

虽然LTD治疗类风湿性关节炎的疗效很好,但缺乏基础的实验研究,其调节免疫反应网络、促进滑膜炎症消退的具体作用机制尚不清楚。

 

目的:探究LTD是否能通过调节ILC2的免疫应答机制促进RA滑膜炎症的消退。

方法:根据文献描述,构建了胶原诱导型(CIA)的关节炎小鼠模型,随后用LTD(27.75 g/kg/d)灌胃干预28天。增强免疫后,每7天取小鼠后肢桡骨矢状面,用游标卡尺测量小鼠后肢跖关节厚度;每7天进行CIA关节炎严重程度评分。

取所有小鼠右后肢分别进行HE染色TRAP染色番红O染色,观察滑膜炎症、软骨破坏和骨侵蚀的组织病理学变化并进行评估评分。免疫荧光检测F4/80、CD206、iNOS2含量。ELISA试剂盒检测RA产生的IFN-γ、IL-17、IL-4的含量。

结果:干预后CIA小鼠关节肿胀、滑膜炎症浸润及关节软骨破坏均有所减轻。Th17炎症细胞的增殖分化及促炎细胞因子IL-17、IFN-γ的分泌受到抑制。此外,LTD还可以激活ILC2分泌抗炎细胞因子IL-4,激活STAT6信号通路,并与Treg细胞协同作用,抑制M1型巨噬细胞在滑膜组织中的浸润,促进其向M2表型转化。

结论:LTD被证明是治疗类风湿性关节炎的有效中药配方,能减轻CIA小鼠关节炎症肿胀,抑制滑膜组织炎症浸润,减轻软骨损伤。主要的机制可能与调节ILC2s和Th细胞的增殖,调节JAK / STAT信号通路的激活,促进M1巨噬细胞转换为抗炎M2表型,抑制炎性因子的分泌有关。这些研究结果为进一步补充LTD治疗包括RA在内的自身免疫性关节炎提供了基础。LTD可以作为RA治疗的辅助或替代

文献来源:

Zhang H, Liu J, Zhang P, et al. (2021). Herbal Formula Longteng Decoction Promotes the Regression of Synovial Inflammation in Collagen-Induced Arthritis Mice by Regulating Type 2 Innate Lymphocytes. Frontiers in pharmacology, 12, 778845. https://doi.org/10.3389/fphar.2021.778845

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createdName=chentianping, createdTime=Fri Mar 25 10:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1788465, encodeId=fb141e88465a1, content=<a href='/topic/show?id=38e014162e2' target=_blank style='color:#2F92EE;'>#Pharmacol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14162, encryptionId=38e014162e2, topicName=Pharmacol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=930e243, createdName=dingxiaobo, createdTime=Sat Feb 11 22:26:15 CST 2023, time=2023-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787783, encodeId=b4c51e8778314, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, 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target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290066, encodeId=56e4129006672, content=<a href='/topic/show?id=fe5c40e26d1' target=_blank style='color:#2F92EE;'>#固有淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40726, encryptionId=fe5c40e26d1, topicName=固有淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cbcc223, createdName=cooco, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302429, encodeId=69a713024291c, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1379511, encodeId=7e3d13e95111c, content=<a href='/topic/show?id=09e46655974' target=_blank style='color:#2F92EE;'>#滑膜炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66559, encryptionId=09e46655974, topicName=滑膜炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a98f453, createdName=pcw106, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=)]
    2023-02-24 jj000001
  5. [GetPortalCommentsPageByObjectIdResponse(id=1996460, encodeId=fec519964608a, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Tue Sep 20 13:26:15 CST 2022, time=2022-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908691, encodeId=d5cd1908691a4, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, 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target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290066, encodeId=56e4129006672, content=<a href='/topic/show?id=fe5c40e26d1' target=_blank style='color:#2F92EE;'>#固有淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40726, encryptionId=fe5c40e26d1, topicName=固有淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cbcc223, createdName=cooco, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302429, encodeId=69a713024291c, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1379511, encodeId=7e3d13e95111c, content=<a href='/topic/show?id=09e46655974' target=_blank style='color:#2F92EE;'>#滑膜炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66559, encryptionId=09e46655974, topicName=滑膜炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a98f453, createdName=pcw106, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=)]
    2022-03-31 医者仁者

    #中医#太表浅了

    0

  6. 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createdName=chentianping, createdTime=Fri Mar 25 10:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1788465, encodeId=fb141e88465a1, content=<a href='/topic/show?id=38e014162e2' target=_blank style='color:#2F92EE;'>#Pharmacol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14162, encryptionId=38e014162e2, topicName=Pharmacol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=930e243, createdName=dingxiaobo, createdTime=Sat Feb 11 22:26:15 CST 2023, time=2023-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787783, encodeId=b4c51e8778314, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, 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target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290066, encodeId=56e4129006672, content=<a href='/topic/show?id=fe5c40e26d1' target=_blank style='color:#2F92EE;'>#固有淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40726, encryptionId=fe5c40e26d1, topicName=固有淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cbcc223, createdName=cooco, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302429, encodeId=69a713024291c, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1379511, encodeId=7e3d13e95111c, content=<a href='/topic/show?id=09e46655974' target=_blank style='color:#2F92EE;'>#滑膜炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66559, encryptionId=09e46655974, topicName=滑膜炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a98f453, createdName=pcw106, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=)]
    2022-03-25 lmm397
  7. 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target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290066, encodeId=56e4129006672, content=<a href='/topic/show?id=fe5c40e26d1' target=_blank style='color:#2F92EE;'>#固有淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40726, encryptionId=fe5c40e26d1, topicName=固有淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cbcc223, createdName=cooco, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), 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createdName=pcw106, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=)]
  8. 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encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Fri Feb 24 16:26:15 CST 2023, time=2023-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207514, encodeId=d11e120e514a9, content=<a href='/topic/show?id=c01b2138812' target=_blank style='color:#2F92EE;'>#中医#</a>太表浅了, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21388, encryptionId=c01b2138812, topicName=中医)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=医者仁者, createdTime=Thu Mar 31 13:03:03 CST 2022, time=2022-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266427, encodeId=80fc126642e1d, content=<a href='/topic/show?id=57a53011364' target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290066, encodeId=56e4129006672, content=<a href='/topic/show?id=fe5c40e26d1' target=_blank style='color:#2F92EE;'>#固有淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40726, encryptionId=fe5c40e26d1, topicName=固有淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cbcc223, createdName=cooco, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302429, encodeId=69a713024291c, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1379511, encodeId=7e3d13e95111c, content=<a href='/topic/show?id=09e46655974' target=_blank style='color:#2F92EE;'>#滑膜炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66559, encryptionId=09e46655974, topicName=滑膜炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a98f453, createdName=pcw106, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=)]
  9. [GetPortalCommentsPageByObjectIdResponse(id=1996460, encodeId=fec519964608a, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Tue Sep 20 13:26:15 CST 2022, time=2022-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908691, encodeId=d5cd1908691a4, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, 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encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Fri Feb 24 16:26:15 CST 2023, time=2023-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207514, encodeId=d11e120e514a9, content=<a href='/topic/show?id=c01b2138812' target=_blank style='color:#2F92EE;'>#中医#</a>太表浅了, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21388, encryptionId=c01b2138812, topicName=中医)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=医者仁者, createdTime=Thu Mar 31 13:03:03 CST 2022, time=2022-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266427, encodeId=80fc126642e1d, content=<a href='/topic/show?id=57a53011364' target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1290066, encodeId=56e4129006672, content=<a href='/topic/show?id=fe5c40e26d1' target=_blank style='color:#2F92EE;'>#固有淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40726, encryptionId=fe5c40e26d1, topicName=固有淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cbcc223, createdName=cooco, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=), 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createdName=pcw106, createdTime=Fri Mar 25 06:26:15 CST 2022, time=2022-03-25, status=1, ipAttribution=)]
    2022-03-25 pcw106

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