Later phase cardioprotection of ischemic post-conditioning against ischemia/reperfusion injury depends on iNOS and PI3K-Akt pathway

被引:3
作者
Wang, Gongming [1 ]
Li, Xin [1 ]
Wang, Hong [2 ]
Wang, Yan [1 ]
Zhang, Ligong [1 ]
Zhang, Le [1 ]
Liu, Bei [1 ]
Zhang, Mengyuan [1 ]
机构
[1] Shandong Univ, Shandong Prov Hosp, Dept Anesthesiol, 324 Jingwu Rd, Jinan 250021, Peoples R China
[2] Taian Cent Hosp, Dept Nephrol, Tai An 271000, Shandong, Peoples R China
来源
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH | 2015年 / 7卷 / 12期
基金
中国国家自然科学基金;
关键词
Delayed cardioprotection; ischemic post-conditioning; ischemia-reperfusion injury; phosphatidylinositol; 3-kinase; Akt; inducible nitric oxide synthase; MITOCHONDRIAL PERMEABILITY TRANSITION; NITRIC-OXIDE SYNTHASE; MYOCARDIAL-INFARCTION; REPERFUSION INJURY; RAT HEARTS; PORE; NEUTROPHILS; DYSFUNCTION; INHIBITION; EXPRESSION;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The cardioprotection of ischemic post-conditioning (IPO) has been well demonstrated after a short period of reperfusion. However, little is known about the long-term effects of IPO. This study aimed to investigate the long term cardioprotection of IPO in a rat myocardial ischemia/reperfusion model and to explore the potential mechanism. Methods and results: Rats were either sham-operated (Sham group) or underwent 30-min left anterior descending coronary artery ischemia followed by immediate reperfusion (I/R group) or post-conditioning with 5 cycles of 10-s ischemia and 10-s reperfusion (IPO group). At 24 h after reperfusion, infarct size reduced from 34.7 +/- 1.1% in I/R group to 24.9 +/- 1.3% in IPO group (P<0.05) and the iNOS expression in IPO group was 4.7-fold higher than in I/R group. iNOS inhibitor 1400 W (1 mg/kg, 5 min before postconditioning or reperfusion) prevented the increase in iNOS expression and abolished IPO-induced protection (34.4 +/- 1.0%, P>0.05 vs. I/R group). When rats were treated with PI3K inhibitor LY294002 5 min before reperfusion (0.3 mg/kg), p-Akt expression at R 3 h and iNOS expression at R 24 h were significantly inhibited. Moreover, the delayed infarct-sparing effect of IPO was absent in the presence of LY294002. Conclusion: IPO has prolonged cardioprotective effects and iNOS as an important downstream effector of PI3K-Akt pathway contributes to the delayed phase cardioprotection of IPO.
引用
收藏
页码:2603 / 2611
页数:9
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