Inhibition of dynamin-related protein 1 has neuroprotective effect comparable with therapeutic hypothermia in a rat model of cardiac arrest
Inhibition of dynamin-related protein 1 has neuroprotective effect comparable with therapeutic hypothermia in a rat model of cardiac arrest
复制标题
在心脏骤停的大鼠模型中，抑制动力相关蛋白 1 具有与低温治疗相当的神经保护作用。
DOI：
10.1016/j.trsl.2018.01.002
复制
发表时间：
2018-04-01
影响因子：
7.8
通讯作者：
Tang, Wanchun
中科院分区：
文献类型：
--
作者：
Wang, Peng;Li, Yi;Tang, Wanchun
动力蛋白相关蛋白1 （Dynamin-related protein 1, Drp1）调节线粒体分裂，已经证明mdivi-1抑制Drp1可提高生存率，减轻脑缺血损伤和心脏骤停。在这项研究中，我们比较了Drp1抑制和低温治疗对心脏骤停大鼠复苏后神经损伤的影响。将大鼠随机分为4组：mdiv -1治疗组（n = 39）、低温组（n = 38）、常温组（n = 41）、假手术组（n = 12）。mdivi-1治疗组大鼠于恢复自然循环（ROSC）后1分钟静脉滴注mdivi-1 1.2 mg/kg。低温组大鼠在复苏后5分钟开始快速冷却，保持体核温度在33±0.5℃持续2小时。结果显示，抑制Drp1和低温治疗均可增加3天存活时间（均P < 0.05），并改善心脏骤停后72小时的神经功能。此外，抑制Drp1和治疗性低温均可减少海马氨角区和脑线粒体的细胞损伤和凋亡！心脏骤停后的功能障碍包括三磷酸腺苷生成、活性氧和线粒体膜电位。此外，治疗性低温降低了线粒体！Drp1表达与线粒体！心脏骤停后的裂变。综上所述，在心脏骤停大鼠模型中，抑制Drp1对复苏后神经系统预后的影响与治疗性低温相似，并且治疗性低温的神经保护作用与抑制线粒体裂变有关。
Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, it has been proven that inhibition of Drp1 by mdivi-1 improves survival and attenuates cerebral ischemic injury offer cardiac arrest. In this study, we compared the effects of Drp1 inhibition with therapeutic hypothermia on post-resuscitation neurologic injury in a rat model of cardiac arrest. Rats were randomized into 4 groups: mdivi-1 treatment group (n = 39), hypothermic group (n = 38), normothermic group (n = 41), and sham group (n = 12). The rats in the mdivi-1 treatment group were received intravenously 1.2 mg/kg of mdivi-1 at 1 minute after the return of spontaneous circulation (ROSC). In rats in hypothermia group, rapid cooling was initiated at 5 minutes after resuscitation, and the core temperature was maintained to 33 +/- 0.5 degrees C for 2 hours. The results showed that both Drp1 inhibition and therapeutic hypothermia increased 3-day survival time (all P < 0.05) and improved neurologic function up to 72 hours post cardiac arrest. In addition, both Drp1 inhibition and therapeutic hypothermia decreased cell injury, apoptosis in hippocampal cornu ammonis 1 region and brain mitochondria! dysfunction including adenosine triphosphate production, reactive oxygen species and mitochondrial membrane potential after cardiac arrest. Moreover, therapeutic hypothermia decreased mitochondria! Drp1 expression and mitochondria! fission after cardiac arrest. In conclusion, inhibition of Drp1 has a similar effect to therapeutic hypothermia on neurologic outcome after resuscitation in this cardiac arrest rat model, and the neuroprotective effects of therapeutic hypothermia are associated with inhibition of mitochondrial fission.