Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice.
Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice.
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自噬参与远端肢体缺血后处理对正常小鼠（而非糖尿病小鼠）心肌缺血/再灌注损伤的心脏保护作用
DOI：
10.1371/journal.pone.0086838
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Han Z;Cao J;Song D;Tian L;Chen K;Wang Y;Gao L;Yin Z;Fan Y;Wang C
背景最近的动物研究和临床试验数据表明，远程肢体缺血后处理（RIPostC）可以引起有效的心脏保护作用。然而，在缺血再灌注损伤（IR）过程中，RIPostC对糖尿病（DM）患者和非糖尿病患者心肌的影响和机制尚不清楚。自噬在减轻心肌缺血再灌注损伤中起重要作用。本研究旨在观察RIPostC对糖尿病及非糖尿病小鼠心肌缺血再灌注损伤模型的影响，并探讨自噬在这一过程中的作用。方法与结果建立了链脲佐菌素（STZ）诱导的DM小鼠模型和心肌IR模型。使用非侵入性技术，在正常小鼠（ND）和DM小鼠中通过左后肢中的三个循环的缺血（5分钟）和再灌注（5分钟）诱导RIPostC。在ND组中，RIPostC显著减小梗死面积（ND-RIPostC中32.6±3.0%对ND-IR中50.6±2.4%，p<0.05）并改善心脏射血分数（ND-RIPostC中49.70±3.46%对ND-IR中31.30±3.95%，p<0.05）。DM组未见RIPostC介导的心肌保护作用。为了分析自噬的作用，进行蛋白质印迹和免疫组织化学。结果显示，ND-RIPostC组中分离体1（SQSTM 1/p62）水平降低，Beclin-1水平升高，LC 3-II/LC 3-I比值升高，而DM-RIPostC组无此变化。结论RIPostC对正常小鼠IR具有心肌保护作用，而对DM小鼠无保护作用，其机制可能与上调自噬有关。
Background Recent animal study and clinical trial data suggested that remote limb ischemic postconditioning (RIPostC) can invoke potent cardioprotection. However, during ischemia reperfusion injury (IR), the effect and mechanism of RIPostC on myocardium in subjects with or without diabetes mellitus (DM) are poorly understood. Autophagy plays a crucial role in alleviating myocardial IR injury. The aim of this study was to determine the effect of RIPostC on mice myocardial IR injury model with or without DM, and investigate the role of autophagy in this process. Methodology and Results Streptozocin (STZ) induced DM mice model and myocardial IR model were established. Using a noninvasive technique, RIPostC was induced in normal mice (ND) and DM mice by three cycles of ischemia (5 min) and reperfusion (5 min) in the left hindlimb. In ND group, RIPostC significantly reduced infarct size (32.6±3.0% in ND-RIPostC vs. 50.6±2.4% in ND-IR, p<0.05) and improved cardiac ejection fraction (49.70±3.46% in ND-RIPostC vs. 31.30±3.95% in ND-IR, p<0.05). However, in DM group, no RIPostC mediated cardioprotetion effect was observed. To analyze the role of autophagy, western blot and immunohistochemistry was performed. Our data showed that a decreased sequestosome 1 (SQSTM1/p62) level, an increased Beclin-1 level, and higher ratio of LC3-II/LC3-I were observed in ND RIPostC group, but not DM RIPostC group. Conclusions The current study suggested that RIPostC exerts cardioprotection effect on IR in normal mice, but not DM mice, and this difference is via, at least in part, the up-regulation of autophagy.
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影响因子：
5.3
作者：
Lekli I;Ray D;Mukherjee S;Gurusamy N;Ahsan MK;Juhasz B;Bak I;Tosaki A;Gherghiceanu M;Popescu LM;Das DK
通讯作者：
Das DK
DOI：
10.1152/ajpheart.00379.2008
发表时间：
2008-10-01
影响因子：
4.8
作者：
Bouhidel, Omar;Pons, Sandrine;Ghaleh, Bijan
通讯作者：
Ghaleh, Bijan
影响因子：
10.8
作者：
Gurusamy, Narasimman;Lekli, Istvan;Das, Dipak K.
通讯作者：
Das, Dipak K.
影响因子：
5.5
作者：
Qi, Zhi-Feng;Luo, Yu-Min;Ji, Xun-Ming
通讯作者：
Ji, Xun-Ming
影响因子：
0.6
作者：
Janosi Andras;Ofner Peter;Dinya Elek
通讯作者：
Dinya Elek