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外周热损伤导致大鼠早期血脑屏障功能障碍和基质金属蛋白酶表达。

Peripheral thermal injury causes early blood-brain barrier dysfunction and matrix metalloproteinase expression in rat.

作者信息

Berger Jamie, Sprague Shane M, Wu Yimin, Davis William W, Jimenez David F, Barone Constance M, Ding Yuchuan

机构信息

Division of Plastic and Reconstructive Surgery, The University of Texas Health Science Center at San Antonio, Floyd C Drive, San Antonio, TX 78229-3900, USA.

出版信息

Neurol Res. 2007 Sep;29(6):610-4. doi: 10.1179/016164107X172158.

Abstract

High mortality incidence after serious systemic thermal injury is believed to be linked to significant increases in cerebral permeability, ultimately leading to irreversible blood-brain barrier (BBB) breakdown. The aim of this study was to investigate whether disruption of microvascular integrity in a rat thermal injury model is associated with early matrix metalloproteinase (MMP) expression. A total of 35 Sprague-Dawley rats were studied in thermal injury and control groups, each group containing two subgroups, one for brain edema and Evans blue analysis and another for MMP mRNA analysis. Thermally injured animals were anesthetized and submerged vertically in 85 degrees C water to the neck for 6 seconds producing a third degree burn affecting 70% of the total body surface area. BBB integrity was determined by measuring amount of Evans blue after 7 hours of injury with a spectrophotometer. Brain edema was detected by calculating water content. Brain mRNA levels were determined with real-time PCR 3 and 7 hours post-injury. Brain water content was significantly increased after peripheral injury at hour 7. Evans blue leakage was also significantly increased at the same time, suggesting an impaired BBB function after injury. Expressions of MMP-2 and MMP-9 mRNA in brain were increased as early as 3 hours after injury and remained at hour 7. Our study demonstrated a significant increase in cerebral permeability that occurs after serious systemic thermal injury. The underlying mechanisms could be related to early expression of MMPs.

摘要

严重全身性热损伤后的高死亡率被认为与脑通透性显著增加有关,最终导致不可逆的血脑屏障(BBB)破坏。本研究的目的是调查大鼠热损伤模型中微血管完整性的破坏是否与早期基质金属蛋白酶(MMP)表达有关。总共35只Sprague-Dawley大鼠被分为热损伤组和对照组进行研究,每组包含两个亚组,一个用于脑水肿和伊文思蓝分析,另一个用于MMP mRNA分析。将热损伤动物麻醉后垂直浸入85摄氏度的水中至颈部6秒,造成占全身表面积70%的三度烧伤。在损伤7小时后用分光光度计测量伊文思蓝的量来确定BBB的完整性。通过计算含水量来检测脑水肿。在损伤后3小时和7小时用实时PCR测定脑mRNA水平。在损伤后第7小时外周损伤后脑含水量显著增加。同时伊文思蓝渗漏也显著增加,表明损伤后BBB功能受损。脑内MMP-2和MMP-9 mRNA的表达在损伤后3小时就开始增加,并在7小时时仍保持增加。我们的研究表明,严重全身性热损伤后会出现脑通透性显著增加。其潜在机制可能与MMPs的早期表达有关。

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