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首页> 外文期刊>Experimental Physiology >Hyperbaric oxygenation and 20‐hydroxyeicosatetreanoic acid inhibition reduce stroke volume in female diabetic Sprague–Dawley rats
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Hyperbaric oxygenation and 20‐hydroxyeicosatetreanoic acid inhibition reduce stroke volume in female diabetic Sprague–Dawley rats

机译：高压氧合和20-羟基杂辛酸抑制减少女性糖尿病Sprague-Dawley大鼠中风体积

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摘要

New Findings What is the central question of this study? Is there a beneficial effect and what are the mechanisms of acute and multiple hyperbaric oxygenation (HBO 2 ) exposures on the outcome of cerebral tissue injury induced by a transient middle cerebral artery occlusion model in diabetic female rats? Are 20‐hydroxyeicosatetreanoic acid and epoxyeicosatrienoic acids involved? What is the main finding and its importance? Equal reduction of cortical and total infarct size in rats treated with HBO 2 and HET0016 (20‐hydroxyeicosatetreanoic acid production inhibitor) and significant mRNA upregulation of epoxyeicosatrienoic acid‐producing enzymes (Cyp2J3 and Cyp2C11) in treated groups suggest that HBO 2 and HET0016 are highly effective stroke treatments and that cytochrome P450 metabolites are involved in this therapeutic effect. We evaluated the effects of acute and repetitive hyperbaric oxygenation (HBO 2 ), 20‐hydroxyeicosatetreanoic acid (20‐HETE) inhibition by N ‐hydroxy‐ N ′‐(4‐butyl‐2methylphenyl)‐formamidine (HET0016) and their combination on experimental stroke outcomes. Streptozotocin‐induced type?1 diabetic Sprague–Dawley female rats ( n ?=?42; n ?=?7 per group), were subjected to 30?min of transient middle cerebral artery occlusion (t‐MCAO)–reperfusion and divided into the following groups: (1) control group, without treatment; and groups exposed to: (2) HBO 2 ; (3) multiple HBO 2 (HBO 2 immediately and second exposure 12?h after t‐MCAO); (4) HET0016 pretreatment (1?mg?kg ?1 , 3?days before t‐MCAO) combined with HBO 2 after t‐MCAO; (5) HET0016 treatment (1?h before, during and for 6?h after t‐MCAO); and (6) HET0016 treatment followed by HBO 2 after t‐MCAO. Messenger RNA expression of CYP2J3, CYP2C11, CYP4A1, endothelial nitric oxide synthase and epoxide hydrolase 2 was determined by real‐time qPCR. Cortical infarct size and total infarct size were equally and significantly reduced in HBO 2 ‐ and HET0016‐treated rats. Combined treatment with HET0016 and HBO 2 provided no significant additive effect compared with HET0016 treatment only. Messenger RNA of Cyp2J3 was significantly increased in all study groups, and mRNA of Cyp2C11 was significantly increased in the multiple HBO 2 group and the HET0016 treatment followed by HBO 2 group, compared with the control group. Expression of endothelial nitric oxide synthase was significantly increased after HBO 2 treatments, and expression of epoxide hydrolase 2 was increased in all groups compared with the control group. In diabetic female Sprague–Dawley rats, HBO 2 and HET0016 are highly effective stroke treatments, suggesting the involvement of cytochrome P450 metabolites and the NO pathway in this therapeutic effect.
机译：新发现这项研究的核心问题是什么？是否存在有益的效果，急性和多种高压氧合（HBO 2）曝光的机制是对糖尿病雌性大鼠瞬时中脑动脉闭塞模型诱导的脑组织损伤的结果的影响。是20-羟基喹硫代酸和环氧二亚硅酸亚甲酸吗？主要发现和重要性是什么？用HBO 2和HET0016（20-羟基喹臭酸产生抑制剂）处理的大鼠皮质和总梗塞大小的平均梗死大小和在处理基团中产生的环氧基硅醛酸的酶（CYP2J3和CYP2C11）的显着mRNA上调表明HBO 2和HET0016高度有效的卒中治疗和细胞色素P450代谢物参与这种治疗效果。我们评估了急性和重复高压氧合（HBO 2），20-羟基喹硫吡啶酸（20-HETE）抑制（4-丁基-2-甲基苯基） - 甲酰脒（HET0016）及其对实验组合的影响的影响中风结果。链脲佐菌素诱导的类型？1糖尿病Sprague-Dawley雌性大鼠（n？= 42;每组N？= 7 = 7），经过30？min的瞬时中脑动脉闭塞（T-MCAO） - 重量并分成以下组：（1）对照组，无需治疗;和暴露于：（2）HBO 2; （3）多个HBO 2（HBO 2立即和第二次曝光12？H后T-MCAO）; （4）HET0016预处理（1？mg？kg？1,3？t-mcao之前）与t-mcao之后与hbo 2合并; （5）HET0016治疗（1？H之前，期间和6？H在T-MCAO之后）; （6）HET0016治疗后，T-MCAO后HBO 2。通过实时QPCR测定CYP2J3，CYP2C11，CYP4A1，内皮一氧化物合酶和环氧化物水解酶2的信使RNA表达。皮质梗塞尺寸和总梗塞尺寸同样且显着降低了HBO 2 - 和HET0016处理的大鼠。与HET0016和HBO 2的组合治疗没有仅与HET0016治疗相比没有显着的添加剂效果。所有研究组中CYP2J3的信使RNA显着增加，与对照组相比，在多个HBO 2组和HET0016治疗中，CYP2C11的mRNA显着增加，然后是HBO 2组。在HBO 2处理后，内皮大氧化氮合酶的表达显着增加，与对照组相比，所有组中环氧化物水解酶2的表达增加。在糖尿病雌性Sprague-Dawley大鼠中，HBO 2和HET0016是高效的卒中处理，表明细胞色素P450代谢物和NO途径在这种治疗效果中的累积。

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  • 来源
    《Experimental Physiology》 |2017年第12期|共11页
  • 作者

    Mi?ir Mihael; Reni? Marija; Novak Sanja; Mihalj Martina; ?osi? Anita; Vesel Monika; Drenjan?evi? Ines;

  • 作者单位

    Clinical Hospital Center OsijekNeurology ClinicOsijek Croatia;

    Croatian Institute for Brain ResearchSchool of Medicine University of ZagrebZagreb Croatia;

    University Josip Juraj Strossmayer Osijek Faculty of Medicine Osijek Department of Physiology and;

    University Josip Juraj Strossmayer Osijek Faculty of Medicine Osijek Department of Physiology and;

    University Josip Juraj Strossmayer Osijek Faculty of Medicine Osijek Department of Physiology and;

    University Josip Juraj Strossmayer Osijek Faculty of Medicine Osijek Department of Physiology and;

    University Josip Juraj Strossmayer Osijek Faculty of Medicine Osijek Department of Physiology and;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 人体生理学;
  • 关键词

    brain ischemia; stroke; hyperbaric oxygenation; diabetes mellitus;

    机译：脑缺血;中风;高压氧合;糖尿病;

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