Polydatin post-treatment alleviates myocardial ischaemia/reperfusion injury by promoting autophagic flux
Polydatin post-treatment alleviates myocardial ischaemia/reperfusion injury by promoting autophagic flux
复制标题
虎杖甙后处理可通过促进自噬通量减轻心肌缺血/再灌注损伤。
DOI：
10.1042/cs20160082
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发表时间：
2016-09-01
期刊：
影响因子：
6
通讯作者：
Chen, Aihua
中科院分区：
文献类型：
--
作者：
Ling, Yuanna;Chen, Guiming;Chen, Aihua
虎杖苷是白藜芦醇的一种糖苷，具有比白藜芦醇更强的抗氧化作用。已知RES是一种自噬增强剂，对缺血/再灌注(I/R)损伤具有心脏保护作用。然而，PD治疗后对心肌I/R损伤的影响尚不清楚。在本研究中，我们研究了PD后处理对心肌I/R损伤和自噬的影响。C57BL/6小鼠结扎左冠状动脉(LCA)，低氧培养的新生大鼠心肌细胞(NRCs)在再灌流或复氧过程中给予赋形剂或PD处理。我们注意到，PD在I/R或缺氧/复氧(H/R)时增强自噬并减少细胞凋亡，这种作用可被携带Beclin 1短发夹状RNA的腺病毒和自噬抑制剂3-甲基腺嘌呤(3-MA)共同处理而被拮抗。与赋形剂处理的小鼠相比，PD处理的小鼠的心肌梗死面积(IS)显著减小，左室短轴缩短率(LVFS)和射血分数(EF)显著升高，但这些作用可被3-MA部分逆转。此外，在Pd处理的NRCS中，串联荧光MRFP-GFP-LC3检测显示自噬小体被大量清除，自噬通量增加，并且与溶酶体抑制剂Bafilmycin A1(Baf)共同处理表明Pd促进了自溶酶体的降解。此外，Pd后处理降低NRCS线粒体膜电位和细胞内活性氧(ROS)的产生，这些作用可被Baf部分阻断。这些结果表明，PD后处理通过促进自噬通量清除受损的线粒体来减少ROS和细胞死亡，从而限制心肌I/R损伤。
Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation. We noted that PD enhanced autophagy and decreased apoptosis during I/R or hypoxia/reoxygenation (H/R), and this effect was antagonized by co-treatment with adenovirus carrying short hairpin RNA for Beclin 1 and 3-methyladenine (3-MA), an autophagic inhibitor. Compared with vehicle-treated mice, PD-treated mice had a significantly smaller myocardial infarct size (IS) and a higher left ventricular fractional shortening (LVFS) and ejection fraction (EF), whereas these effects were partly reversed by 3-MA. Furthermore, in the PD-treated NRCs, tandem fluorescent mRFP-GFP-LC3 assay showed abundant clearance of autophagosomes with an enhanced autophagic flux, and co-treatment with Bafilomycin A1 (Baf), a lysosomal inhibitor, indicated that PD promoted the degradation of autolysosome. In addition, PD post-treatment reduced mitochondrial membrane potential and cellular reactive oxygen species (ROS) production in NRCs, and these effects were partially blocked by Baf. These findings indicate that PD post-treatment limits myocardial I/R injury by promoting autophagic flux to clear damaged mitochondria to reduce ROS and cell death.