Research progress of PAR-2 in myocardial ischemia/reperfusion injury mediated by autophagy
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摘要: 心肌再灌注治疗是急性心肌梗死最重要的治疗方法之一, 能够显著改善致死、致残率。但再灌注早期仍难以避免增加心肌损害, 引起心肌缺血/再灌注 (ischemia/reperfusion, I/R) 损伤。心肌缺血阶段激活的自噬对心肌具有保护作用, 而再灌注阶段激活的自噬对心肌具有损害作用, 其机制可能与缺血阶段AMPK-mTOR信号通路, 以及再灌注阶段Bcl-2-Beclin 1信号通路介导的自噬诱导I/R损伤的重要途径有关。蛋白酶激活受体2 (protease activated receptor2, PAR-2) 在缺血心肌细胞高度表达, 是自噬的上游标记物之一, 能够显著改善I/R损伤, 具有心肌保护作用。在缺血阶段, PAR-2可能通过激活AMPK途径, 抑制其下游mTOR表达, 从而激活自噬, 保护心肌;在再灌注阶段, 通过Bcl-2下调激活Beclin 1表达, 诱导自噬发生, 并且能够上调Bcl-2mRNA表达水平。本文就PAR-2对自噬介导的I/R损伤的研究进展进行综述。
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关键词:
- 蛋白酶激活受体2 /
- 自噬 /
- 缺血/再灌注 /
- AMPK-mTOR /
- Bcl-2-Beclin1
Abstract: Reperfusion is one of the most important methods in treatment of acute myocardial infartion, and can significantly improve fatality and disability.However, it dose not prevent myocardium damaging in the early stage of reperfusion, which leads to myocardial ischemia and reperfusion (I/R) injury.Autophagy plays a protective role in myocardial ischemia phase but plays an opposite role in myocardial reperfusion phase.The underlying mechanism may be related to the signal pathway of AMPK-mTOR in ischemia phase and the signal pathway of Bcl-2-Bclin1 in reperfusion phase.Protease activated receptor2 (PAR-2) is highly expressed the cells of myocardial ischemia.As one of the upstream markers of autophagy, PAR-2 may be able to significantly reduce the I/R injury and pro-tect myocardium.In myocardial ischemia, PAR-2 plays a protective role through activating the pathway of AMPK and inhibiting the expression of downstream mTOR.During myocardial reperfusion, PAR-2 induces the autophagy by activating the expression of Beclin 1 through the downregulation of Bcl-2 and upregulates the expression of Bcl-2 mRNA.The research progress of PAR-2 in myocardial I/R injury mediated by autophagy is reviewed.-
Key words:
- protease activated receptor 2 /
- autophagy /
- ischemia/reperfusion /
- AMPK-mTOR /
- Bcl-2-Beclin 1
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