Mild hypothermia alleviates excessive autophagy and mitophagy in a rat model of asphyxial cardiac arrest
Mild hypothermia alleviates excessive autophagy and mitophagy in a rat model of asphyxial cardiac arrest
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DOI：
10.1007/s10072-014-1813-6
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发表时间：
2014-11-01
影响因子：
3.3
通讯作者：
Zhu, Chang-Lai
中科院分区：
文献类型：
--
作者：
Lu, Jian;Qian, Hui-Yin;Zhu, Chang-Lai
亚低温是一种有效的治疗策略，以改善心脏骤停（CA）患者的不良神经功能结局。然而，其潜在机制仍不清楚。本研究的目的是评估亚低温对CA大鼠模型海马神经元细胞内自噬和线粒体自噬的影响。采用窒息5 min的方法建立SD大鼠CA模型，复苏成功后，将存活大鼠随机分为常温组（NT）和低温组（HT）。CA后4小时诱导轻度低温（32 A ℃），并以0.5 A ℃/h的速率复温动物。神经功能缺损评分（NDS）用于确定神经功能状态。从海马提取细胞质和线粒体蛋白，并测量LC 3B-II/I和Parkin的表达，分别作为细胞内自噬和线粒体自噬的标志物。在60只接受CA的大鼠中，44只成功复苏（73%），33只存活至实验结束（55%）。亚低温可维持核和线粒体结构的正常形态，显著改善NDS（p < 0.05）。与对照组相比，NT组海马神经细胞LC 3B-Ⅱ/Ⅰ和Parkin蛋白表达明显增加（p < 0.05）。亚低温组LC 3B-II/I和Parkin水平较NT组明显降低（p < 0.05）。缺血/再灌注（I/R）损伤后CA和复苏后，亚低温保护线粒体并改善神经功能，可能是通过减少神经元中过度的自噬和线粒体自噬。
Mild hypothermia is an effective therapeutic strategy to improve poor neurological outcomes in patients following cardiac arrest (CA). However, the underlying mechanism remains unclear. The aim of the study was to evaluate the effect of mild hypothermia on intracellular autophagy and mitophagy in hippocampal neurons in a rat model of CA. CA was induced in Sprague-Dawley (SD) rats by asphyxia for 5 min. After successful resuscitation, the surviving rats were randomly divided into two groups, the normothermia (NT) group and the hypothermia (HT) group. Mild hypothermia (32 A degrees C) was induced following CA for 4 h, and animals were rewarmed at a rate of 0.5 A degrees C/h. Neurologic deficit scores (NDS) were used to determine the status of neurological function. Cytoplasmic and mitochondrial protein from the hippocampus was extracted, and the expression of LC3B-II/I and Parkin were measured as markers of intracellular autophagy and mitophagy, respectively. Of the 60 rats that underwent CA, 44 were successfully resuscitated (73 %), and 33 survived until the end of the experiment (55 %). Mild hypothermia maintained eumorphism of nuclear and mitochondrial structures and significantly improved NDS (p < 0.05). Expression of LC3B-II/I and Parkin in hippocampal nerve cells were significantly increased (p < 0.05) in the NT group relative to the control. Meanwhile, mild hypothermia reduced the level of LC3B-II/I and Parkin (p < 0.05) relative to the NT group. Mild hypothermia protected mitochondria and improved neurological function following CA and resuscitation after ischemia/reperfusion (I/R) injury, likely by reducing excessive autophagy and mitophagy in neurons.