Li Xin, Liu Yong-Jun, Xia Jing-Ming, Zeng Xiao-Yun, Liao Xiao-Xing, Wei Hong-Yan, Hu Chun-Lin, Jing Xiao-Li, Dai Gang
Department of Emergency, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Department of Emergency, the People's Hospital of Guangdong province, Guangzhou 510080, China.
Department of Emergency, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Am J Emerg Med. 2016 Aug;34(8):1511-8. doi: 10.1016/j.ajem.2016.05.007. Epub 2016 May 11.
Recent studies have shown the existence of autophagy in cerebral ischemia; however, there has been no research on the role of autophagy in cerebral injury after cardiopulmonary resuscitation (CPR). This study was conducted to determine the role of autophagy in an animal model of ventricular fibrillation (VF)/CPR.
Experiment 1: A total of 48 adult Wistar rats were untreated for 7 minutes after induction of VF using an external transthoracic alternating current, and subsequent CPR was performed to observe the existence of autophagy after the return of spontaneous circulation (ROSC). Experiment 2: A total of 72 rats were pretreated with intracerebroventricular injection of physiologic saline (control group), the autophagy inducer (rapamycin group), or the autophagy inhibitor 3-methyladenine (3-methyladenine group) before ROSC to evaluate the contribution of autophagy to neuronal injury after ROSC.
The activation of autophagy was attenuated 2 to 4 hours after ROSC, which was related to the activity decrease of 5'-adenosine monophosphate-activated protein kinase after ROSC. Rapamycin treatment significantly increased the expressions of LC3-II and Beclin-1 after ROSC, attenuated the activation of caspase-3, promoted neuronal survival and decreased neuronal apoptosis, and improved the neurologic deficit score after CPR.
The activation of autophagy after ROSC offered a remarkable tolerance to VF/CPR ischemic insult and improved the neurologic outcomes.
近期研究已表明脑缺血中存在自噬；然而，关于心肺复苏（CPR）后脑损伤中自噬的作用尚无研究。本研究旨在确定自噬在室颤（VF）/CPR动物模型中的作用。
实验1：48只成年Wistar大鼠经胸外交流电诱导VF后不处理7分钟，随后进行CPR以观察自主循环恢复（ROSC）后自噬的存在情况。实验2：72只大鼠在ROSC前经脑室内注射生理盐水（对照组）、自噬诱导剂（雷帕霉素组）或自噬抑制剂3 - 甲基腺嘌呤（3 - 甲基腺嘌呤组）进行预处理，以评估自噬对ROSC后神经元损伤的作用。
ROSC后2至4小时自噬激活减弱，这与ROSC后5'-单磷酸腺苷激活蛋白激酶活性降低有关。雷帕霉素处理显著增加了ROSC后LC3 - II和Beclin - 1的表达，减弱了caspase - 3的激活，促进了神经元存活并减少了神经元凋亡，并改善了CPR后的神经功能缺损评分。
ROSC后自噬的激活对VF/CPR缺血性损伤具有显著耐受性，并改善了神经功能结局。
