Department of Cardiovascular Surgery, General Hospital of Shenyang Military Region, 83 Wenhua Road, Shenyang, Liaoning 110016, China.
Department of Pharmacy, General Hospital of Shenyang Military Region, 83 Wenhua Road, Shenyang, Liaoning 110016, China.
Oxid Med Cell Longev. 2018 Feb 13;2018:2750695. doi: 10.1155/2018/2750695. eCollection 2018.
Diabetes exacerbates oxidative/nitrative stress during myocardial ischemia-reperfusion (MI/R) injury. Recent studies highlighted the cardioprotective actions of polydatin. However, its effect on diabetic MI/R injury and the underlying mechanisms remain unknown. This work was undertaken to evaluate the effect of polydatin on diabetic MI/R injury with a focus on Notch1/Hes1 signaling and myocardial oxidative/nitrative stress. Streptozotocin- (STZ-) induced diabetic rats were administered with polydatin (20 mg/kg/d) in the absence or presence of DAPT (a -secretase inhibitor) or LY294002 (a PI3K/Akt inhibitor) and then subjected to MI/R injury. Polydatin administration preserved cardiac function and reduced myocardial infarct size. Moreover, polydatin ameliorated myocardial oxidative/nitrative stress damage as evidenced by decreased myocardial superoxide generation, malondialdehyde, gp91 expression, iNOS expression, NO metabolite level, and nitrotyrosine content and increased eNOS phosphorylation. However, these effects were blocked by DAPT administration. DAPT also inhibited the stimulatory effect of polydatin on the Notch1/Hes1-Pten/Akt signaling pathway in a diabetic myocardium. Additionally, LY294002 not only abolished polydatin's antiapoptotic effect but also reversed its inhibitory effect on myocardial oxidative/nitrative stress. Polydatin effectively reduced MI/R injury and improved left ventricular functional recovery under diabetic condition by ameliorating oxidative/nitrative stress damage. Importantly, Notch1/Hes1-mediated activation of Pten/Akt signaling played a crucial role in this process.
糖尿病会加剧心肌缺血再灌注（MI/R）损伤过程中的氧化/硝化应激。最近的研究强调了虎杖苷的心脏保护作用。然而，其对糖尿病性 MI/R 损伤的影响及其潜在机制仍不清楚。本研究旨在评估虎杖苷对糖尿病性 MI/R 损伤的作用，重点关注 Notch1/Hes1 信号通路和心肌氧化/硝化应激。采用链脲佐菌素（STZ）诱导建立糖尿病大鼠模型，用或不用 DAPT（-分泌酶抑制剂）或 LY294002（PI3K/Akt 抑制剂）预处理后，进行 MI/R 损伤。虎杖苷给药可维持心脏功能，减少心肌梗死面积。此外，虎杖苷可改善心肌氧化/硝化应激损伤，表现为心肌超氧阴离子生成、丙二醛、gp91 表达、iNOS 表达、NO 代谢物水平、硝基酪氨酸含量减少，以及 eNOS 磷酸化增加。然而，这些作用被 DAPT 给药所阻断。DAPT 还抑制了糖尿病心肌中 Notch1/Hes1-Pten/Akt 信号通路对虎杖苷的刺激作用。此外，LY294002 不仅消除了虎杖苷的抗凋亡作用，还逆转了其对心肌氧化/硝化应激的抑制作用。虎杖苷通过改善氧化/硝化应激损伤，有效减轻糖尿病条件下的 MI/R 损伤，改善左心室功能恢复。重要的是，Notch1/Hes1 介导的 Pten/Akt 信号通路的激活在这一过程中起着关键作用。
