Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Gwangju, Korea.
J Cardiovasc Pharmacol Ther. 2012 Dec;17(4):387-94. doi: 10.1177/1074248412438102. Epub 2012 Mar 6.
Curcumin, the active ingredient of turmeric (Curcuma longa), is known to have anti-inflammatory and antioxidative properties. The present study was aimed to determine the effect of curcumin in regional myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the role of prosurvival kinases and apoptotic kinases.
Sprague-Dawley rats (n = 109) subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion followed by reperfusion were assigned to receive saline (control), curcumin (100 mg/kg), wortmannin (inhibitor of phosphatidylinositol-3-OH kinase [PI3K]-Akt), wortmannin + curcumin, U0126 (inhibitor of extracellular signal-regulated kinase [ERK1/2]), U0126 + curcumin, SB216763 (inhibitor of glycogen synthase kinase [GSK-3β]), and SB216763 + curcumin 20 minutes before LAD occlusion. Infarct size was measured after 2 hours of reperfusion by triphenyl tetrazolium chloride staining. The phosphorylation of Akt, ERK1/2, GSK-3β, p38, and c-Jun N-terminal kinases (JNK) was determined by immunoblotting after 10 minutes of reperfusion.
Curcumin significantly reduced the infarct size compared with the control (33.1% ± 6.2% vs 50.1% ± 3.9%; P < .05). Wortmannin or U0126 alone did not affect the infarct size but abolished the curcumin-induced cardioprotective effect. Curcumin significantly enhanced the phosphorylation of Akt, ERK1/2, and GSK-3β, while it reduced that of p38 and JNK. Wortmannin or U0126 abolished enhanced phosphorylation of GSK-3β induced by curcumin. SB216763 alone or combined with curcumin reduced the infarct size and enhanced phosphorylation of GSK-3β compared with the control.
Preconditioning by curcumin effectively protects against regional myocardial I/R injury through the activation of prosurvival kinases involving PI3K-Akt, ERK1/2, and GSK-3β, and attenuation of p38 and JNK.
姜黄素是姜黄（Curcuma longa）的活性成分，具有抗炎和抗氧化作用。本研究旨在确定姜黄素对局部心肌缺血/再灌注（I/R）损伤的影响及其潜在机制，包括存活相关激酶和凋亡激酶的作用。
将 109 只 Sprague-Dawley 大鼠进行 30 分钟左前降支冠状动脉（LAD）闭塞后再灌注，随机分为盐水（对照组）、姜黄素（100mg/kg）、wortmannin（磷脂酰肌醇-3-羟激酶[PI3K]-Akt 抑制剂）、wortmannin+姜黄素、U0126（细胞外信号调节激酶[ERK1/2]抑制剂）、U0126+姜黄素、SB216763（糖原合酶激酶[GSK-3β]抑制剂）和 SB216763+姜黄素组，在 LAD 闭塞前 20 分钟给予相应药物。再灌注 2 小时后用氯化三苯基四氮唑染色测量梗死面积。再灌注 10 分钟后通过免疫印迹法测定 Akt、ERK1/2、GSK-3β、p38 和 c-Jun N 末端激酶（JNK）的磷酸化水平。
与对照组相比，姜黄素显著减少梗死面积（33.1%±6.2%比 50.1%±3.9%；P<0.05）。wortmannin 或 U0126 单独使用不影响梗死面积，但可消除姜黄素的心脏保护作用。姜黄素显著增强 Akt、ERK1/2 和 GSK-3β的磷酸化，同时降低 p38 和 JNK 的磷酸化。wortmannin 或 U0126 消除了姜黄素诱导的 GSK-3β的磷酸化增强。SB216763 单独或与姜黄素联合使用可减少梗死面积并增强 GSK-3β的磷酸化，与对照组相比。
姜黄素预处理可通过激活存活相关激酶（包括 PI3K-Akt、ERK1/2 和 GSK-3β），减轻 p38 和 JNK，有效防止局部心肌 I/R 损伤。
