Therapeutic hypothermia attenuates global cerebral reperfusion-induced mitochondrial damage by suppressing dynamin-related protein 1 activation and mitochondria-mediated apoptosis in a cardiac arrest rat model
Therapeutic hypothermia attenuates global cerebral reperfusion-induced mitochondrial damage by suppressing dynamin-related protein 1 activation and mitochondria-mediated apoptosis in a cardiac arrest rat model
复制标题
在心脏骤停大鼠模型中，低温治疗通过抑制动力相关蛋白 1 激活和线粒体介导的细胞凋亡来减轻全脑再灌注引起的线粒体损伤
DOI：
10.1016/j.neulet.2017.02.065
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发表时间：
2017-04-24
影响因子：
2.5
通讯作者：
Xu, Jianguo
中科院分区：
文献类型：
--
作者：
Fan, Jingjing;Cai, Shenquan;Xu, Jianguo
低温治疗可有效减轻心脏骤停后的脑缺血/再灌注 (I/R) 损伤，并且已提出多种机制。动力相关蛋白 1 (Drp1) 是动力超家族中的一个大型 GTP 酶，主要控制线粒体裂变，并与 IR 诱导的 Cyt C 释放和细胞凋亡相关。然而，低温治疗对心脏骤停后 Drpl 和线粒体分裂的影响仍不清楚。在本研究中，非心脏骤停和心脏骤停后大鼠接受6小时常温（37-38℃）或治疗性低温（32-34℃），并在心脏骤停后6小时和72小时收获海马。结果显示，心脏骤停后 Drpl 和 Cyt C 的表达增加，但治疗性低温在心脏骤停后 6 小时部分逆转了这种增加。透射电子显微镜（TEM）还显示心脏骤停后低温治疗后形态的变化。此外，低温治疗可以减少组织病理学损伤，抑制CA1神经元凋亡，改善心脏骤停后72小时的存活率和神经系统结果。综上所述，我们的研究表明，低温治疗对全脑 liR 损伤具有神经保护作用，这至少部分归因于抑制 Drpl 和 Cyt C 表达以及保护线粒体结构。 (C) 2017 Elsevier B.V. 保留所有权利。
Therapeutic hypothermia is effective to attenuate brain ischemia/reperfusion (I/R) injury after cardiac arrest, and multiple mechanisms have been proposed. Dynamin-related protein 1 (Drp1), a large GTPases of dynamin superfamily, predominantly controls mitochondrial fission and is related to IR-induced Cyt C release and apoptosis. However, the effect of therapeutic hypothermia on Drpl and mitochondrial fission after cardiac arrest remains still unclear. In this study, non-cardiac arrest and post-cardiac arrest rats received 6-h normothermia (37-38 degrees C) or therapeutic hypothermia (32-34 degrees C), and the hippocampus was harvested at 6 h and 72 h after cardiac arrest. Results showed the expression of Drpl and Cyt C increased after cardiac arrest, but therapeutic hypothermia partially reversed this increase at 6 h after cardiac arrest. Transmission electron microscopy (TEM) also showed a change in morphology following therapeutic hypothermia after cardiac arrest. Moreover, therapeutic hypothermia could decrease the histopathological damage, inhibit the apoptosis of CA1 neurons and improve the survival and neurological outcomes at 72 h after cardiac arrest. Taken together, our study demonstrates that therapeutic hypothermia is neuroprotective against global cerebral liR injury, which is, at least partially, ascribed to the inhibition Drpl and Cyt C expression and the protection of mitochondrial structure. (C) 2017 Elsevier B.V. All rights reserved.