Activation of autophagy improved the neurologic outcome after cardiopulmonary resuscitation in rats

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• 作者：Xin Li ; MD^a ; ^b ; ¹ ; Yong-jun Liu ; MD^a ; ¹ ; Jing-Ming Xia ; MD^c ; Xiao-yun Zeng ; MD^a ; Xiao-Xing Liao ; PhD^a ; Hong-Yan Wei ; MD^a ; ¹ ; Chun-Lin Hu ; MD^a ; ^{hu-chunlin@163.com" class="auth_mail" title="E-mail the corresponding author} ; Xiao-Li Jing ; Post-Graduate^a ; Gang Dai ; Bachelor's Degree^d
• 刊名：The American Journal of Emergency Medicine
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：34
• 期：8
• 页码：1511-1518
• 全文大小：1161 K

文摘

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.

Methods

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.

Results

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.

Conclusions

The activation of autophagy after ROSC offered a remarkable tolerance to VF/CPR ischemic insult and improved the neurologic outcomes.