中文摘要：

Doxorubicin (纪录影片) 是主要 anticancer 化学疗法的代理人。然而，它由于 cardiomyocyte apoptosis 的副作用引起心肌症。我们以前报导了 angiopoietin-1 显著地在 ischemic 损害以后减少了心肌的梗塞并且保护了 cardiomyocytes 免受氧化导致压力的 apoptosis 的伤害。angiopoietin-1 可以保护 cardiomyocytes 免受导致纪录影片的 apoptosis 的伤害，这被假设。Cardiomyocytes H9C2 是有表示 angiopoietin-1 (Ad5-Ang-1 ) 的侵入人体气管粘膜的病菌的 transfected 在房间前的 24 h 在 2 mol/L 的集中与纪录影片被质问。Ad5-GFP 用作向量控制。Cardiomyocyte apoptosis 用染色的 Annexin V-FITC 和 caspase-3 被评估， caspase-8 活动被西方的弄污决定。结果证明纪录影片处理显著地导致了由 Annexin V-FITC 的更大的数字证实了的 cardiomyocyte apoptosis 在 caspase-3 和 caspase-8 活动的染色的房间和增加。相反， angiopoietin-1 的 overexpression 显著地阻止了导致纪录影片的 cardiomyocyte apoptosis。阐明 angiopoietin-1 由保护了房间免受导致纪录影片的 apoptosis 的伤害的机制，我们分析了表明小径的外来、内在的 apoptotic。我们观察到 angiopoietin-1 阻止了表明小径的外来、内在的 apoptotic 的导致纪录影片的激活。明确地， angiopoietin-1 在 FasL 和 Bax 层次阻止了导致纪录影片的增加并且在 H9C2 房间劈开 caspase-3 和 caspase-8 层次。另外， angiopoietin-1 的 overexpression 也激活支持幸存的 phosphoinositide-3 kinase (PI3K )/Akt 发信号小径和减少的导致纪录影片的原子 factor-kappaB (NF-B ) 激活。我们的数据建议支持 angiopoietin-1 的表示能是为减少导致纪录影片的 cardiomyocyte cytoxicity 的一条潜在的途径。

英文摘要：

Doxorubicin （Dox） is a major anticancer chemotherapeutic agent. However, it causes cardiomyopathy due to the side effect of cardiomyocyte apoptosis. We have previously reported that angiopoietin-1 significantly reduced myocardial infarction after ischemic injury and protected cardiomyocytes from oxidative stress-induced apoptosis. It is hypothesized that angiopoietin-1 may protect cardiomyocytes from Dox-induced apoptosis. Cardiomyocytes H9C2 were transfected with adenovirus expressing angiopoietin-1 （Ad5-Ang-1） 24 h before the cells were chal- lenged with Dox at a concentration of 2 ~tmol/L. Ad5-GFP served as the vector control. Cardiomyocyte apoptosis was evaluated using Annexin V-FITC staining and caspase-3 and caspase-8 activity was determined by Western blotting. The results showed that Dox treatment significantly induced cardiomyocyte apoptosis as evidenced by the greater number of Annexin V-FITC stained cells and increases in caspase-3 and caspase-8 activity. In contrast, overexpression of angiopoietin-1 significantly prevented Dox-induced cardiomyocyte apoptosis. To elucidate the mechanisms by which angiopoietin-1 protected cells from Dox-induced apoptosis, we analyzed both extrinsic and intrinsic apoptotic signaling pathways. We observed that angiopoietin-1 prevented Dox-induced activation of both extrinsic and intrinsic apoptotic signaling pathways. Specifically, angiopoietin-1 prevented DOX-induced in- creases in FasL and Bax levels and cleaved caspase-3 and caspase-8 levels in H9C2 cells. In addition, overexpres- sion of angiopoietin-1 also activated the pro-survival phosphoinositide-3 kinase （PI3K）/Akt signaling pathway and decreased Dox-induced nuclear factor-kappaB （NF-~：B） activation. Our data suggest that promoting the expression of angiopoietin-1 could be a potential approach for reducing Dox-induced cardiomyocyte cytoxicity.