摘要
目的:本研究的目的是评估缺血/再灌注(I / R)暴露后,遗传上增加肌浆网Ca2 + -ATPase(Serca2a)表达对心脏损伤的影响及相关机制。 方法和结果:大鼠左冠状动脉前降支(LAD)闭塞30分钟,然后24小时再灌注。心脏功能分析显示,与野生型(WT)大鼠相比,Serca2a转基因大鼠(Serca2aTG)大鼠的心脏功能显着改善。与WT组相比,Serca2aTG大鼠的心肌梗死面积明显缩小。与WT大鼠相比,Serca2aTG大鼠的Bcl-2表达降低;但是I / R后,Serca2aTG大鼠的Bcl-2表达显着增加。另外,与I / R后WT组相比,Serca2aTG大鼠Bax明显下调。同时,Serca2aTG组自噬标记物LC-3B增加,而WT组只有p62增加,而Serca2aTG组没有增加。电镜观察证实,I / R后Serca2aTG组自噬体较WT组大鼠多。 结论:我们的研究结果表明,Serca2a的过度表达在I / R损伤和缺血后功能恢复的心肌保护中起重要作用,可能是通过抗坏死,抗凋亡和自噬信号通路。我们的研究为长期过表达Serca2a的心力衰竭患者提供了坚实的基础数据和临床治疗的新视角。
关键词: 心脏保护,缺血再灌注(I / R),肌浆网Ca2 + -ATPase(Serca2a),细胞凋亡,自噬。
Current Gene Therapy
Title:Cardioprotective Effects of Serca2a Overexpression Against Ischemiareperfusion- induced Injuries in Rats
Volume: 17 Issue: 3
关键词: 心脏保护,缺血再灌注(I / R),肌浆网Ca2 + -ATPase(Serca2a),细胞凋亡,自噬。
摘要: Aims: The aim of the present study was to assess how genetically increased Sarcoplasmic reticulum Ca2+-ATPase (Serca2a) expression affects cardiac injury after Ischemia/Reperfusion (I/R) exposure and the related mechanisms involved.
Methods and Results: Rats were subjected to Left Anterior Descending coronary artery (LAD) occlusion for 30 min followed by a 24-hour reperfusion. Cardiac function analysis revealed that cardiac function dramatically improved in Serca2a transgenic rats, (Serca2aTG) rats, compared to Wild Type (WT) rats. Serca2aTG rats developed a significantly smaller myocardial infarction size compared to those in WT group. The expression of the Bcl-2 was lower in Serca2aTG rats compared with WT rats; but, Bcl-2 expression was markedly increased in Serca2aTG rats compared with WT after I/R. In addition, Bax was markedly downregulated in Serca2aTG rats compared to WT group after I/R. Meanwhile, autophagy marker LC-3B was increased in Serca2aTG group, and p62 was only increased in WT group but not in Serca2aTG group in response to I/R. Electron microscope observation confirmed that there were more autophagosomes in Serca2aTG group than in WT rats after I/R.
Conclusion: our findings demonstrated that the overexpression of Serca2a plays an important role in myocardial protection from I/R injury and postischemic functional recovery, which may be via antinecrotic, anti-apoptotic and pro-autophagy signal pathways. Our research provides solid basic data and new perspective on clinical treatment in heart failure patients with long-term over-expression of Serca2a.
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Cardioprotective Effects of Serca2a Overexpression Against Ischemiareperfusion- induced Injuries in Rats, Current Gene Therapy 2017; 17 (3) . https://dx.doi.org/10.2174/1566523217666171110175251
DOI https://dx.doi.org/10.2174/1566523217666171110175251 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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