• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Chimeric SOD2/3 inhibits at the endothelial-neutrophil interface to limit vascular dysfunction in ischemia-reperfusion.
【24h】

Chimeric SOD2/3 inhibits at the endothelial-neutrophil interface to limit vascular dysfunction in ischemia-reperfusion.

机译：嵌合的SOD2 / 3抑制内皮细胞-中性粒细胞界面，以限制缺血再灌注中的血管功能障碍。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

After an ischemic episode, reperfusion causes profound oxidative stress in the vasculature of the afflicted tissue/organ. The dysregulated accumulation of reactive oxygen species (ROS), such as superoxide, has been closely linked to the production and release of proinflammatory mediators, a profound increase in adhesion molecule expression by the vascular endothelium, and infiltration of neutrophils during ischemia-reperfusion (I/R). Superoxide dismutase (SOD) has been shown to protect tissues and organs against I/R-induced injury; however, the drug had to be continuously perfused or kidneys had to be occluded to prevent clearance. We used intravital microscopy, a system that allowed us to visualize neutrophil-endothelial interactions within the mesenteric postcapillary venules of cats subjected to I/R and tested the hypothesis that I/R-induced neutrophil recruitment was inhibited by treatment with SOD2/3. SOD2/3 is a chimeric fusion gene product that contains the mature SOD2 as well as the COOH-terminal "tail" of SOD3 and, unlike the three naturally occurring SODs (SOD1, SOD2, and SOD3), which bear a net negative charge at pH 7.4, SOD2/3 is positively charged and physiologically stable. Our results suggest that not only does SOD2/3 have a much greater efficacy in vivo than the native human SOD2, but its administration prevents I/R-induced neutrophil-endothelial cell interactions and microvascular dysfunction. Moreover, our data support the hypothesis that reactive oxidants mediate I/R-induced injury and that the chimeric recombinant SOD2/3 has the potential to be a therapeutic agent against this debilitating illness.
机译：缺血发作后，再灌注会在患病组织/器官的脉管系统中引起强烈的氧化应激。活性氧（ROS）（例如超氧化物）的失调积累与促炎性介质的产生和释放，血管内皮细胞粘附分子表达的大量增加以及缺血再灌注过程中嗜中性白细胞的浸润密切相关（I / R）。超氧化物歧化酶（SOD）已被证明可以保护组织和器官免受I / R诱导的伤害。但是，必须连续灌注药物，或者必须阻塞肾脏以防止清除。我们使用了活体显微镜检查法，该系统使我们能够观察接受I / R的猫的肠系膜毛细血管后微静脉内的中性粒细胞-内皮相互作用，并检验了用SOD2 / 3处理抑制I / R诱导的中性白细胞募集的假设。 SOD2 / 3是一种嵌合融合基因产物，它包含成熟的SOD2和SOD3的COOH末端“尾巴”，并且与三种天然存在的SOD（SOD1，SOD2和SOD3）不同，后者在pH 7.4时，SOD2 / 3带正电且生理稳定。我们的结果表明，SOD2 / 3不仅在体内具有比天然人SOD2更高的功效，而且其给药可防止I / R诱导的中性粒细胞-内皮细胞相互作用和微血管功能障碍。此外，我们的数据支持以下假设，即反应性氧化剂介导I / R诱导的损伤，并且嵌合重组SOD2 / 3有潜力成为对抗这种衰弱性疾病的治疗剂。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号