Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering, Ministry of Education, Zhejiang University, Hangzhou, PR China.
Planta Med. 2011 Jul;77(10):984-91. doi: 10.1055/s-0030-1250718. Epub 2011 Jan 31.
In this study, we provide new evidence that orientin from bamboo leaves (Phyllostachys nigra) protect H9c2 cardiomyocytes against ischemia/reperfusion (I/R) injury through the mitochondrial apoptotic pathway. A previous work has identified that orientin could protect myocardium against ischemia/reperfusion injury. Mitochondria are both critical determinants of cardioprotection and crucial targets of cardioprotective signaling. Their role during reperfusion is conspicuously critical because the conditions promote apoptosis through the mitochondrial pathway and necrosis though irreversible damage to mitochondria, which is in association with mitochondrial permeability transition (MPT). After myocardial ischemia, opening of the mPTP is a critical determinant of cell death. The relationship of orientin and mPTP in mediating reperfusion-induced cardiomyocytes injury is still elusive. Here, our results indicate that the protective effect of orientin in H9c2 cells subjected to I/R injury is associated with depression of the mPTP opening, resultant mitochondrial dysfunction, and apoptosis. Further investigation of cellular mechanisms revealed that these effects were associated with inhibition of reactive oxygen species (ROS) generation, repolarization of mitochondrial membrane potential (Δψ(m)), suppression of mitochondrial cytochrome C release, enhancement of the Bcl-2 level, and inhibition of Bax and Smac/DIABLO levels. Furthermore, these beneficial effects of orientin were blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, and orientin could enhance Akt phosphorylation. In summary, we demonstrate that orientin protects H9c2 cardiomytocytes against I/R-induced apoptosis by modulating the mPTP opening, and this role of orientin may involve the PI3K/Akt signaling pathway.
在这项研究中，我们提供了新的证据表明竹叶黄酮通过线粒体凋亡途径保护 H9c2 心肌细胞免受缺血/再灌注（I/R）损伤。先前的工作已经确定，竹叶黄酮可以保护心肌免受缺血/再灌注损伤。线粒体是决定心肌保护作用的关键因素，也是心肌保护信号的重要靶点。它们在再灌注期间的作用至关重要，因为再灌注条件通过线粒体途径促进细胞凋亡，通过对线粒体的不可逆损伤导致坏死，这与线粒体通透性转换（MPT）有关。心肌缺血后，mPTP 的开放是细胞死亡的关键决定因素。竹叶黄酮在介导再灌注诱导的心肌细胞损伤中与 mPTP 的关系仍不清楚。在这里，我们的研究结果表明，竹叶黄酮对 H9c2 细胞 I/R 损伤的保护作用与抑制 mPTP 开放、线粒体功能障碍和细胞凋亡有关。进一步的细胞机制研究表明，这些作用与抑制活性氧（ROS）生成、线粒体膜电位（Δψ(m)）复极化、抑制线粒体细胞色素 C 释放、增强 Bcl-2 水平以及抑制 Bax 和 Smac/DIABLO 水平有关。此外，PI3K 抑制剂wortmannin 阻断了竹叶黄酮的这些有益作用，并且竹叶黄酮可以增强 Akt 的磷酸化。总之，我们证明了竹叶黄酮通过调节 mPTP 开放来保护 H9c2 心肌细胞免受 I/R 诱导的凋亡，而竹叶黄酮的这种作用可能涉及 PI3K/Akt 信号通路。
