晚期糖基化终末产物受体介导急性缺氧诱导的早期生长反应因子-1表达上调  

Receptor for advanced glycation end-products may mediate the upregulation of hypoxia-induced early growth response-1 in mouse aorta

作　　者：黄春[1] 杨明[1] 施晓芸[1] 陈晓春[1] 

机构地区：[1]福建医科大学协和医院老年科,福州350001

出　　处：《中华老年医学杂志》2013年第4期444-447,共4页Chinese Journal of Geriatrics

摘　　要：目的探讨急性缺氧对早期生长反应因子-1（Egr-1）和单核细胞趋化蛋白-1（MCP-1）表达的影响及其可能的信号机制。方法取整体缺氧小鼠模型的主动脉，实时定量反转录聚合酶链反应（RT-PCR）检测Egr-1和MCP-1mRNA含量、蛋白印迹检测Egr-1和晚期糖基化终末产物受体（RAGE）抗原表达，凝胶迁移或电泳迁移率实验（EMSA）检测Egr-1DNA结合活性；以可溶性RAGE（sRAGE）阻断RAGE信号后，观察其对缺氧诱导Egr-1表达的影响。结果缺氧30min，Egr-1mRNA表达上调，为对照组的（28．3±0．9）倍（F=617．17，P〈0．01）；缺氧45min，Egr-1的抗原含量为对照组的（5．7±0．3）倍（F=57．18，P〈0．01），Egr-1DNA结合活力高于对照组，并被抗-Egr-1IgG所抑制；缺氧4h，MCP-1mRNA含量为对照组的（4．O±0．3）倍（F=30．68，P〈0．01）；缺氧15min，RAGE抗原含量增加，sRAGE预处理减少缺氧诱导的Egr-1表达（3．3±0．2）倍与（1．4±0．2）倍（F=30．20，P〈0．01）。结论小鼠整体缺氧诱导主动脉Egr-1及MCP-1表达上调，阻断RAGE信号显著抑制缺氧诱导的Egr-1高表达。Objective To investigate the impact of hypoxia on the expression of early growth response-l（Egr-1） and monocyte chemoattractant protein-1 （MCP-1） in mouse aorta, and to probe the underlying mechanism involving receptor for advanced glycation end-products （RAGE）. Methods 3-month-old C57BL/6 mice were subjected to hypoxia [（6.0±0.5））% oxygen] to establish the global hypoxia model（n= 6 rats for each）. Aortas were dissected, Egr-1 mRNA and MCP-1 mRNA were detected by real time RT-PCR, Egr-1 and RAGE proteins were tested by Western blot, and Egr-1 DNA binding activity was assayed by electrophoretic mobility shift assay （EMSA）. For blockade of RAGE, mice were pretreated with soluble RAGE （sRAGE） for 1 h by intra-peritoneal injection before they were exposed to hypoxia. Mice with normoxia were used as controls. Results After 30 minutes of hypoxic exposure, Egr-1 mRNA in aorta was increased to （28. 3±0.9）folds compared with normoxic controls （F= 617.17,P〈0.01）, and the induction persisted for at least 3 hours. After 45 minutes of hypoxic exposure, Egr-1 proteins in aorta was increased to （5.7±0. 3） folds compared with normoxic controls （F = 57.18, P〈 0.01）;the enhanced DNA binding activity of Egr-1 by hypoxia was attenuated by pretreatment with anti-Egr-1 IgG. After 4 hours of hypoxic exposure, MCP-1 mRNA expression in aorta was increased to（4.0 ± 0.3）folds compared with normoxic controls （F= 30.68,P〈0.01）. RAGE antigen was increased significantly within 30 minutes of hypoxic exposure,with the peak at 15 minutes; hypoxia-induced Egr-1 mRNA expression was significantly attenuated by pretreatment with sRAGE （3.3± 0.2） folds compared with normoxic controls （F = 30.20, P 〈 0.01）. Conclusions Hypoxia significantly induces Egr-1 and MCP-1 upregulation expressions in mouse aorta, and blockade of RAGE significantly attenuates hypoxia-induced Egr-1 expression. These findings suggest RAGE signaling is involved in hypoxia-induced vascular inflammatory stress

关 键 词：缺氧 糖基化终产物 高级 早期生长反应蛋白质 

分 类 号：R54[医药卫生—心血管疾病]