Anesthesiology：miR-21对于ISO抗缺血再灌注损伤心肌保护作用的意义

2015-08-15 张森译 MedSci原创

基础与临床研究都已表明：麻醉预处理可有效减少心肌损伤，即便是在缺血前很短的时间中给予患者挥发性麻醉药异氟烷（ISO），亦可通过抗缺血再灌注（I/R）损伤而发挥心肌保护作用，然而具体的机制尚未完全阐明。MicroRNAs是一条大约22个核苷酸长度的内源性，非编码的单链RNA分子，在机体中参与了大量生理与病理生理过程的调节。研究发现MicroRNA-21 (miR-21)在心肌细胞，心脏成纤

基础与临床研究都已表明：麻醉预处理可有效减少心肌损伤，即便是在缺血前很短的时间中给予患者挥发性麻醉药异氟烷（ISO），亦可通过抗缺血再灌注（I/R）损伤而发挥心肌保护作用，然而具体的机制尚未完全阐明。MicroRNAs是一条大约22个核苷酸长度的内源性，非编码的单链RNA分子，在机体中参与了大量生理与病理生理过程的调节。

研究发现MicroRNA-21 (miR-21)在心肌细胞，心脏成纤维细胞、血管内皮细胞和血管平滑肌细胞中高度表达，并参与心肌细胞的生长及死亡,调节心肌成纤维细胞功能以及血管平滑肌细胞的增殖和凋亡。近期的研究表明,miR-21与急性心肌I/R损伤密切相关：（1）在发生缺氧、缺血时，心肌细胞中的miR-21将会上调；（2）miR-21的下调使心肌细胞更易受到I/R损伤的损害，然而miR-21表达增加可以增强心肌细胞对I/R损伤的耐受性；（3）miR-21抑制剂可以减弱缺血预处理的心肌保护作用。本研究使用miR-21基因敲除（KO）小鼠，旨在探讨miR-21对于ISO抗缺血再灌注损伤心肌保护作用的意义。

通过超声心动图对C57BL/6 及 microRNA-21基因敲除小鼠进行检测。在给予小鼠缺血处理前，给予/不给于小鼠1个最低肺泡有效浓度的异氟烷麻醉，小鼠心脏在30min缺血处理后进行2h再灌注（体内或体外）。通过蛋白质印迹分析对心脏Akt蛋白质分子,内皮一氧化氮合酶(eNOS)和神经元一氧化氮合酶(nNOS)蛋白质进行测定。光刺激产生的氧化应激可以诱导心肌细胞线粒体通透性转换孔（mPTP）打开，使用共焦显微镜观察四甲基乙基酯荧光的迅速消散可对其进行检测。

miR-21基因的缺失并没有改变左心室的表现型，基线心功能，风险区域，以及磷酸化-Akt/Akt，磷酸化-eNOS/eNOS以及磷酸化-nNOS/nNOS的比率。与对照组（54±10%）相比，异氟烷（36±10%）减少了心肌梗死的面积(P<0.05)，并且改善了再灌注后的心功能，增加了缺血再灌注损伤C57BL/6小鼠的磷酸化-Akt/Akt，磷酸化-eNOS/eNOS以及磷酸化-nNOS/nNOS的比率。异氟醚对microRNA-21基因敲除小鼠则不具有以上有益作用。在C57BL/6 及 microRNA-21基因敲除小鼠的分离心肌细胞中，光刺激产生的氧化应激诱导mPTP打开的时间没有显著差异。异氟烷显著延迟了C57BL/6小鼠心肌细胞mPTP的打开，但是microRNA-21基因敲除小鼠则不然。

本研究表明：异氟烷可通过microRNA-21依赖的机制保护缺血再灌注损伤小鼠心肌细胞，并且 Akt/NOS/mPTP通路参与了microRNA-21调控的异氟烷心肌保护作用。

原始出处：

Shigang Qiao,Jessica M.Olson,Mark Paterson,B.S.,Yasheng Yan,B.S.,Ivan Zaja,B.S.,Yanan Liu,Matthias L.Riess,Judy R.Kersten,Mingyu Liang,David C.Warltier,Zeljko J.Bosnjak,Zhi-Dong Ge.MicroRNA-21 Mediates Isoflurane-induced Cardioprotection against Ischemia–Reperfusion Injury via Akt/Nitric Oxide Synthase/Mitochondrial Permeability Transition Pore Pathway. Anesthesiology. 2015 Aug 7

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2016-09-15 1e10c84am36(暂无匿称)

文章不错，值得拜读

59 0
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2015-10-03 12498e5fm12(暂无昵称)

#心肌保护#

53 0
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2015-09-14 dongjia2020

#miR-21#

27 0
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2015-08-26 xiangyuzhou971

#EST#

32 0
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2016-03-30 忠诚向上

好好学习一下

175 0
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2016-03-30 忠诚向上

好好学习一下

110 0
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2016-03-30 忠诚向上

好好学习一下

109 0
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2016-03-30 忠诚向上

好好学习一下

109 0
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2016-03-30 忠诚向上

好好学习一下

58 0
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2016-03-30 忠诚向上

好好学习一下

129 0

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