Arthritis Rheumatol:胰岛素抵抗通路与类风湿性关节炎的疾病活动性有关

2019-12-17 xiangting MedSci原创

这项研究旨在探讨胰岛素抵抗通路在类风湿性关节炎的炎症和疾病靶向治疗中的作用。 在一个爱尔兰RA队列中评估了RA疾病活动性和心血管危险因素,其中包括胰岛素抵抗和体重指数(BMI)。通过免疫组化评估RA和OA滑膜组织中的GLUT1和GLUT4活性。通过ELISA定量离体RA滑膜外植体促炎介质的自发释放和原发性滑膜成纤维细胞(RA SFC)细胞培养上清。蛋白印迹分析激活的AMPK(P‐AMPK)和GL

这项研究旨在探讨胰岛素抵抗通路在类风湿性关节炎的炎症和疾病靶向治疗中的作用。

在一个爱尔兰RA队列中评估了RA疾病活动性和心血管危险因素,其中包括胰岛素抵抗和体重指数(BMI)。通过免疫组化评估RAOA滑膜组织中的GLUT1GLUT4活性。通过ELISA定量离体RA滑膜外植体促炎介质的自发释放和原发性滑膜成纤维细胞(RA SFC)细胞培养上清。蛋白印迹分析激活的AMPKP‐AMPK)和GLUT1蛋白表达。使用细胞外通量分析评估细胞的糖酵解和氧化磷酸化。

胰岛素抵抗与BMI0.113,0.059-0.167p <0.001n = 61)和SJC280.114,0.032-0.197p = 0.008n = 61)独立相关。与OA滑膜相比,RAGLUT1表达增加(p = 0.0003n = 2616),在衬里、亚衬里和血管区域的表达也增加。与之相反,与OA衬里层相比,观察到RAGLUT4表达降低(p = 0.0358n = 218)。在二甲双胍存在的情况下,SFC中的GLUT1蛋白表达降低,而P‐AMPK蛋白表达升高(n = 4)。在RA SFC中(n = 7)二甲双胍增加糖酵解活性(p <0.05),并降低OxPhosp<0.05)。存在二甲双胍或AICAR会降低RA滑膜外植体和SFCsIL-6IL-8MCP-1的自发产生(n= 5-7)。

胰岛素抵抗与RA患者的BMI和滑膜炎显著相关,表明RA中的葡萄糖可利用性与炎症之间存在明显的相互作用。此外,二甲双胍对促炎机制的作用表明,AMPK修饰化合物可用于治疗RA

原始出处:

Lorna Gallagher. Insulin Resistant Pathways are associated with Disease Activity in Rheumatoid Arthritis and are Subject to Disease Modification through Metabolic Reprogramming; A Potential Novel Therapeutic Approach. Arthritis Rheumatol. 16 December 2019.

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    2020-10-08 baoya
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  5. [GetPortalCommentsPageByObjectIdResponse(id=1750118, encodeId=7c1f1e501181e, content=<a href='/topic/show?id=be7c8385345' target=_blank style='color:#2F92EE;'>#胰岛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83853, encryptionId=be7c8385345, topicName=胰岛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a7a536274692, createdName=baoya, createdTime=Thu Oct 08 05:58:00 CST 2020, time=2020-10-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1723987, encodeId=ea4c1e23987d3, content=<a href='/topic/show?id=2d996516e7c' target=_blank style='color:#2F92EE;'>#活动性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65167, encryptionId=2d996516e7c, topicName=活动性)], attachment=null, authenticateStatus=null, createdAvatar=null, 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  6. 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createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Thu Dec 19 01:58:00 CST 2019, time=2019-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1357334, encodeId=77de135e334c0, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Thu Dec 19 01:58:00 CST 2019, time=2019-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1483636, encodeId=539f1483636b8, content=<a href='/topic/show?id=55a6100826cc' target=_blank style='color:#2F92EE;'>#风湿性关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100826, encryptionId=55a6100826cc, topicName=风湿性关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c237911872, createdName=ms1467340776200723, createdTime=Thu Dec 19 01:58:00 CST 2019, time=2019-12-19, status=1, ipAttribution=)]
    2019-12-19 lmm397
  7. 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    2019-12-19 zhaojie88
  9. 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