J Ethnopharmacol:瘀血痹片通过抑制LOX/Ras/Raf-1信号抑制实验性类风湿关节炎血管生成

2022-08-17 紫菀款冬 MedSci原创

评估瘀血痹片(YXB)的抗血管生成活性,并探讨其在胶原诱导型关节炎(CIA)大鼠和VEGF诱导的HUVEC中的作用机制。

背景:瘀血痹片(YXB)主要用于瘀血阻络的痹证,是临床上广泛用于治疗类风湿关节炎(RA)、关节炎等疾病的常用药物。在RA的进展过程中,血管生成在促进炎性细胞的产生方面起着核心作用导致滑膜增生和骨破坏。然而,YXB是否RA进展过程中减弱血管生成仍有待确定。

目的:旨在评估YXB的抗血管生成活性,并探讨其在胶原诱导型关节炎(CIA)大鼠和VEGF诱导的HUVEC中的作用机制。

方法:采用转录调控网络分析和网络药理学方法探讨YXB在RA血管生成中的作用机制。

通过确定关节炎发生率、评分和显微CT分析,评估YXB的抗关节炎效果。通过组织学和免疫组织化学分析评估YXB在体内的抗血管生成作用

通过伤口愈合、细胞迁移、细胞侵袭和血管形成实验评估YXB的体外抗血管生成作用。采用免疫印迹和免疫组化分析探讨YXB的分子机制

结果:YXB降低了CIA大鼠的疾病严重程度并改善了病理特征。YXB显著减少骨破坏和滑膜血管生成。YXB有效抑制了血管生成标记物CD31和VEGF的表达。

在体外,YXB有效抑制HUVEC迁移、侵袭和血管形成。

在确定转录表达谱后,构建并分析了“YXB推定靶点已知RA相关基因与YXB治疗效果相关的基因”相互作用网络。此后,参与RA血管生成的LOX/Ras/Raf-1信号轴被确定为YXB抗RA的候选机制之一。

实验验证中,YXB剂量依赖性地降低CIA大鼠LOX、Ras和Raf-1的表达水平,以及MEK和ERK的磷酸化,这些效果优于甲氨蝶呤(MTX)的抑制作用。

此外,YXB可能是一种有效的血管生成抑制剂,并在体外显著抑制VEGF诱导的LOX/Ras/Raf-1信号的激活。

结论:YXB可能通过抑制LOX/Ras/Raf-1信号抑制血管生成,从而降低RA的疾病严重程度,减少骨侵蚀。YXB或可成为抗血管生成候选药物。此外,调节LOX/Ras/Raf-1信号通路可能是抑制RA和其他自身免疫性疾病血管生成的有效策略。

 

文献来源:

Su X, Yuan B, Tao X, et al. Anti-angiogenic effect of YuXueBi tablet in experimental rheumatoid arthritis by suppressing LOX/Ras/Raf-1 signaling [published online ahead of print, 2022 Aug 8]. J Ethnopharmacol. 2022;115611. doi:10.1016/j.jep.2022.115611

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encryptionId=38e014162e2, topicName=Pharmacol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=930e243, createdName=dingxiaobo, createdTime=Wed May 31 22:47:05 CST 2023, time=2023-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908730, encodeId=937b1908e30e5, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Sun Apr 09 10:47:05 CST 2023, time=2023-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1239245, encodeId=a36c1239245f1, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=99206163724, createdName=ms9000000236829232, createdTime=Wed Aug 17 11:11:34 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266518, encodeId=5bfe126651839, 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=58, 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=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1334418, encodeId=ce601334418d2, content=<a href='/topic/show?id=5306e6164b6' target=_blank style='color:#2F92EE;'>#类风湿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76164, encryptionId=5306e6164b6, topicName=类风湿)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597452, encodeId=ff78159e4522f, content=<a href='/topic/show?id=fa1710082017' target=_blank style='color:#2F92EE;'>#风湿关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100820, encryptionId=fa1710082017, topicName=风湿关节炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=456818510265, createdName=xuruicheng, createdTime=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1787822, encodeId=e6541e8782219, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Sat Apr 15 11:47:05 CST 2023, time=2023-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996502, encodeId=4f451996502c8, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, 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encryptionId=38e014162e2, topicName=Pharmacol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=930e243, createdName=dingxiaobo, createdTime=Wed May 31 22:47:05 CST 2023, time=2023-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908730, encodeId=937b1908e30e5, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Sun Apr 09 10:47:05 CST 2023, time=2023-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1239245, encodeId=a36c1239245f1, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=99206163724, createdName=ms9000000236829232, createdTime=Wed Aug 17 11:11:34 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266518, encodeId=5bfe126651839, 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=58, 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=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1334418, encodeId=ce601334418d2, content=<a href='/topic/show?id=5306e6164b6' target=_blank style='color:#2F92EE;'>#类风湿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76164, encryptionId=5306e6164b6, topicName=类风湿)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597452, encodeId=ff78159e4522f, content=<a href='/topic/show?id=fa1710082017' target=_blank style='color:#2F92EE;'>#风湿关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100820, encryptionId=fa1710082017, topicName=风湿关节炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=456818510265, createdName=xuruicheng, createdTime=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1787822, encodeId=e6541e8782219, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Sat Apr 15 11:47:05 CST 2023, time=2023-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996502, encodeId=4f451996502c8, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, 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encryptionId=38e014162e2, topicName=Pharmacol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=930e243, createdName=dingxiaobo, createdTime=Wed May 31 22:47:05 CST 2023, time=2023-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908730, encodeId=937b1908e30e5, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Sun Apr 09 10:47:05 CST 2023, time=2023-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1239245, encodeId=a36c1239245f1, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=99206163724, createdName=ms9000000236829232, createdTime=Wed Aug 17 11:11:34 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266518, encodeId=5bfe126651839, 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=58, 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=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1334418, encodeId=ce601334418d2, content=<a href='/topic/show?id=5306e6164b6' target=_blank style='color:#2F92EE;'>#类风湿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76164, encryptionId=5306e6164b6, topicName=类风湿)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597452, encodeId=ff78159e4522f, content=<a href='/topic/show?id=fa1710082017' target=_blank style='color:#2F92EE;'>#风湿关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100820, encryptionId=fa1710082017, topicName=风湿关节炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=456818510265, createdName=xuruicheng, createdTime=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=)]
    2022-08-17 ms9000000236829232

    学习了

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1787822, encodeId=e6541e8782219, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Sat Apr 15 11:47:05 CST 2023, time=2023-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996502, encodeId=4f451996502c8, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=99206163724, createdName=ms9000000236829232, createdTime=Wed Aug 17 11:11:34 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266518, encodeId=5bfe126651839, 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=58, 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=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1334418, encodeId=ce601334418d2, content=<a href='/topic/show?id=5306e6164b6' target=_blank style='color:#2F92EE;'>#类风湿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76164, encryptionId=5306e6164b6, topicName=类风湿)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597452, encodeId=ff78159e4522f, content=<a href='/topic/show?id=fa1710082017' target=_blank style='color:#2F92EE;'>#风湿关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100820, encryptionId=fa1710082017, topicName=风湿关节炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=456818510265, createdName=xuruicheng, createdTime=Wed Aug 17 03:47:05 CST 2022, time=2022-08-17, status=1, ipAttribution=)]
    2022-08-17 lmm397
  8. 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  9. 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