Yeh Chi-Hsiao, Chen Tzu-Ping, Wu Yi-Cheng, Lin Yu-Min, Jing Lin Pyng
Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan.
J Surg Res. 2005 May 1;125(1):109-16. doi: 10.1016/j.jss.2004.11.009.
Following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion, pro-inflammatory cytokines are activated and cause cardiomyocytic injury. Nuclear factor (NF)-kappaB is involved in regulating inflammatory signal transduction. Curcumin inhibits NF-kappaB activation and blocks the inflammatory responses. We studied whether curcumin could decrease myocardial ischemia/reperfusion injury with cardioplegia during CPB and attenuate the appearance of apoptosis of cardiomyocytes.
Rabbits received normal saline (group 1) or curcumin (70 mum/kg, group 2; 100 mum/kg, group 3) injection 2 h before CPB. Total CPB was initiated and cold (4 degrees C) antegrade intermittent crystalloid cardioplegia was delivered every 20 min for 60 min of cardiac arrest. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points and then the reperfused hearts were harvested.
Postoperative elevation of plasma levels of interleukin (IL)-8 (14.5, 0.9, 2.9 times over baseline in groups 1-3, respectively, P < 0.05), IL-10 (201.1, 6.0, 14.9 times over baseline in groups 1-3, respectively, P < 0.05), TNF-alpha (9.4, 3.1, 3.9 times over baseline in groups 1-3, respectively, P < 0.05), and cardiac troponin I (141.2, 14.9, 15.0 times over baseline) significantly decreased in the curcumin groups. Appearance of apoptotic cardiomyocytes significantly decreased in the curcumin groups (5.69 +/- 1.64, 1.51 +/- 0.41, 2.43 +/- 0.49 per 1000 nuclei in groups 1-3, respectively, P < 0.01). The activation of neutrophil in the myocardium, which was measured using myocardial myloperoxidase activity assay, was significantly attenuated in the curcumin group. There was a significant increase in apoptosis-related cleavage fragments of caspase-3 and poly-ADP-ribose polymerase in group 1 compared to the other groups.
Curcumin, an inhibitor of NF-kappaB, ameliorated the surge of pro-inflammatory cytokines during CPB and decreased the occurrence of cardiomyocytic apoptosis after global cardiac ischemia/reperfusion injury.
在体外循环（CPB）及心脏整体缺血再灌注后，促炎细胞因子被激活并导致心肌细胞损伤。核因子（NF）-κB参与调节炎症信号转导。姜黄素可抑制NF-κB的激活并阻断炎症反应。我们研究了姜黄素是否能减轻CPB期间心脏停搏液所致的心肌缺血/再灌注损伤，并减少心肌细胞凋亡的发生。
在CPB前2小时，家兔分别注射生理盐水（第1组）或姜黄素（70μmol/kg，第2组；100μmol/kg，第3组）。启动全CPB，每隔20分钟给予冷（4℃）顺行间断晶体心脏停搏液，共60分钟心脏停搏。家兔脱离CPB并再灌注4小时。在不同时间点采集血液，然后摘取再灌注心脏。
术后血浆白细胞介素（IL）-8水平升高（第1-3组分别比基线高14.5、0.9、2.9倍，P<0.05），IL-10（第1-3组分别比基线高201.1、6.0、14.9倍，P<0.05），肿瘤坏死因子-α（TNF-α）（第1-3组分别比基线高9.4、3.1、3.9倍，P<0.05）以及心肌肌钙蛋白I（比基线高141.2、14.9、15.0倍）在姜黄素组显著降低。姜黄素组凋亡心肌细胞的出现显著减少（第1-3组每1000个细胞核中分别为5.69±1.64、1.51±0.41、2.43±0.49，P<0.01）。使用心肌髓过氧化物酶活性测定法测量，姜黄素组心肌中中性粒细胞的激活显著减弱。与其他组相比，第1组中半胱天冬酶-3和聚ADP-核糖聚合酶的凋亡相关裂解片段显著增加。
NF-κB抑制剂姜黄素改善了CPB期间促炎细胞因子的激增，并减少了心脏整体缺血/再灌注损伤后心肌细胞凋亡的发生。
