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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2016年第6期

页码:

656-659

栏目:

基础研究

出版日期:

2016-07-05

文章信息/Info

Title:

Sevoflurane preconditioning protects cardiac function against ischemia/reperfusion injury through up-regulation of ROS-induced autophagy

作者:

张旭东¹; 任鹏程¹; 高昌俊²; 何印斌¹; 孙 丽¹

(第四军医大学唐都医院:1.全军骨肿瘤研究所,2.麻醉科，陕西 西安 710038)

Author(s):

ZHANG Xu-dong¹;  REN Peng-cheng¹;  GAO Chang-jun²;  HE Yin-bin¹;  SUN Li¹

(1.PLA Bone Tumor Research Institute, 2.Department of Anesthesia, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi, China)

关键词:

七氟烷; 缺血/再灌注; 自噬; 活性氧

Keywords:

sevoflurane;  ischemia/reperfusion;  autophagy;  ROS

分类号:

R726.1

DOI:

-

文献标识码:

A

摘要:

目的 探讨七氟烷(SEVO)对离体大鼠缺血/再灌注(ischemia/reperfusion,I/R)心肌功能的影响及其机制。方法 利用非循环等容灌流装置制备离体大鼠心脏灌注模型。24只雄性SD大鼠随机分为I/R组(缺血30 min，再灌注120 min)，I/R+SEVO组(缺血前给予20 ml/L SEVO预处理10 min)， I/R+SEVO+NAC组，I/R+SEVO+TEMPO组(NAC和TEMPO为氧自由基清除剂，浓度分别为10 μg/ml和10 μmol/L，缺血前处理30 min)。缺血前及再灌后检测活性氧(ROS)含量。缺血后采用Western blot 方法检测自噬相关蛋白LC3-II/I、Beclin1、AMPK的表达和AMPK的磷酸化水平。全程检测血流动力学指标。结果 SEVO预处理增加缺血前心肌ROS的水平(P<0.01)，抑制再灌注期ROS水平(P<0.01)；改善I/R心肌功能(P<0.01)。机制研究发现，SEVO增加AMPK的磷酸化和Bclin1的表达(P<0.01)，上调LC3-II/LC3-I的比值(P<0.01)。该现象可被ROS清除剂NAC或TEMPO抑制(P<0.01)。结论 SEVO预处理改善I/R心肌功能，其机制与ROS介导的自噬作用增强有关。

Abstract:

AIM To investigate the effect and underlying mechanism of sevoflurane (SEVO) on cardiac functions after ischemia/reperfusion. METHODSIsolated rat heart perfusion model was achieved by nonrecirculating isovolumic perfusion apparatus. Twenty four male Sprague Dawley rats were divided randomly into I/R group (30 min ischemia followed by 120 min reperfusion), I/R+SEVO group (anesthetic preconditioning was performed with 2% sevoflurane for 10 min before ischemia), I/R+SEVO+NAC group and I/R+SEVO+TEMPO group (ROS-scavengers, NAC or TEMPO was administered at 30 min before ischemia). Reactive oxygen species (ROS) were determined before ischemia and after reperfusion. Western blot was performed to determine autophagy-relative proteins (including AMPK, P-AMPK, LC3-II/LC3-I and Beclin1) after reperfusion. Hemodynamic parameters including LVDP, LVDEP, ±LV dP/dtmax were determined. RESULTSSEVO preconditioning increased myocardial ROS at baseline but decreased myocardial ROS after reperfusion, which ultimately improved myocardial function. In addition, SEVO promoted AMPK activation, Beclin1 expression, and increased LC3-II/I ratio, which was inhibited by ROS-scavengers, NAC and TEMPO. CONCLUSIONSevoflurane preconditioning improves myocardial function under ischemia/reperfusion and the underlying mechanism is associated with up-regulation of ROS-induced autophagy.

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备注/Memo

备注/Memo:

收稿日期：2015-05-21.
通讯作者：任鹏程，副主任医师，主要从事麻醉对脏器保护作用研究Email：tdrpch@163.com
作者简介：张旭东，主治医生，学士Emial：zxdong@126.com

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更新日期/Last Update: 2016-07-10