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首页> 外文期刊>Experimental Neurology >Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic transformation by inhibiting matrix metalloproteinases in focal cerebral ischemia in rats
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Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic transformation by inhibiting matrix metalloproteinases in focal cerebral ischemia in rats

机译:高压氧预处理通过抑制大鼠局灶性脑缺血中的基质金属蛋白酶抑制高血糖增强的出血性转化

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摘要

Hyperglycemia dramatically aggravates brain infarct and hemorrhagic transformation (HT) after ischemic stroke. Oxidative stress and matrix metalloproteinases (MMPs) play an important role in the pathophysiology of HT. Hyperbaric oxygen preconditioning (HBO-PC) has been proved to decrease oxidative stress and has been demonstrated to be neuroprotective in experimental stroke models. The present study determined whether HBO-PC would ameliorate HT by a pre-ischemic increase of reactive oxygen species (ROS) generation, and a suppression of MMP-2 and MMP-9 in hyperglycemic middle cerebral artery occlusion (MCAO) rats. Rats were pretreated with HBO (100% O2, 2.5atmosphere absolutes) 1h daily for 5days before MCAO. Acute hyperglycemia was induced by an injection of 50% dextrose. Neurological deficits, infarction volume and hemorrhagic volume were assessed 24h and 7days after ischemia. ROS scavenger n-acetyl cysteine (NAC), hypoxia-inducible factor-1α (HIF-1α), inhibitor 2-methoxyestradiol (2ME2) and activator cobalt chloride (CoCl2), and MMP inhibitor SB-3CT were administrated for mechanism study. The activity of MMP-2 and MMP-9, and the expression HIF-1α were measured. HBO-PC improved neurological deficits, and reduced hemorrhagic volume; the expression of HIF-1α was significantly decreased, and the activity of MMP-2 and MMP-9 was reduced by HBO-PC compared with vehicle group. Our results suggested that HBO-PC attenuated HT via decreasing HIF-1α and its downstream MMP-2 and MMP-9 in hyperglycemic MCAO rats.
机译:高血糖在缺血性中风后显着加剧脑梗塞和出血转化(HT)。氧化应激和基质金属蛋白酶(MMPs)在HT的病理生理学中起重要作用。已经证明高压氧预处理(HBO-PC)降低氧化应激,并已证明在实验中风模型中是神经保护。本研究确定了HBO-PC是否通过反应性氧物质(ROS)产生的前缺血性增加,以及在高血糖中脑动脉闭塞(MCAO)大鼠中的MMP-2和MMP-9的抑制。每天用HBO(100%O 2,2.5,绝对)预处理大鼠5天在MCAO之前进行5小时。注射50%葡萄糖诱导急性高血糖。在缺血后24h和7天评估神经系统缺陷,梗死体积和出血量。 ROS清除剂N-乙酰半胱氨酸(NAC),缺氧诱导因子-1α(HIF-1α),抑制剂2-甲氧基雌二醇(2ME2)和活化剂氯化钴(COCL2)和MMP抑制剂SB-3CT进行机理研究。测量MMP-2和MMP-9的活性和表达HIF-1α。 HBO-PC改善神经缺陷,减少出血量; HIF-1α的表达显着降低,通过HBO-PC与载体组相比,MMP-2和MMP-9的活性降低。我们的结果表明,通过降低HIF-1α及其下游MMP-2和MMP-9在高血糖MCAO大鼠中减弱HBO-PC。

著录项

  • 来源
    《Experimental Neurology》 |2013年第null期|共7页
  • 作者单位

    Department of Neurosurgery Loma Linda University School of Medicine Loma Linda CA United States;

    Department of Neurosurgery Loma Linda University School of Medicine Loma Linda CA United States;

    Department of Neurosurgery Loma Linda University School of Medicine Loma Linda CA United States;

    Department of Neurosurgery Loma Linda University School of Medicine Loma Linda CA United States;

    Department of Neurosurgery Loma Linda University School of Medicine Loma Linda CA United States;

    Department of Neurosurgery Loma Linda University School of Medicine Loma Linda CA United States;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

    Hemorrhagic transformation; Hyperbaric oxygen preconditioning; MCAO; MMP-2 and MMP-9;

    机译:出血转化;高压氧气预处理;MCAO;MMP-2和MMP-9;

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