Cardioplegic effect of Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor against ischemia-reperfusion myocardial injury in cardiac surgery

聚（腺苷5-二磷酸核糖）合成酶（PARS）抑制剂对心脏手术中缺血再灌注心肌损伤的心脏停跳作用

基本信息

批准号：
16591421
负责人：
NISHIWAKI Noboru
金额：
$ 2.05万
依托单位：
Kinki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591421/
关键词：
Cardioplegia PARP inhibitor Ischemia-reperfusion injury Oxidative stress 8-OHdG 心筋虚血再灌流障害

项目摘要

Ischemic-reperfusion injury has been one of the most serious problem even in current cardiac surgery. Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury by preventing energy depletion associated with oxidative stress. The purpose of our study was to evaluate the efficacy of a cardioplegic solution containing a PARS inhibitor, 3-aminobenzamide (3-AB), for myocardial protection against ischemia-reperfusion injury caused by cardioplegic arrest.Isolated rat hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution (St.Thomas solution) given at 30-min intervals and then reperfused for 20 min. The hearts of rat in the 3-AB(-) group (n=8) were perfused with a standard cardioplegic solution and terminal warm cardioplegia, whereas the 3-AB(+) group (n=8) received these solutions supplemented with 3-AB (100 microM). Left ventricular function and release of cardiac enzymes were monitored before and after cardioplegic arrest. After reperfusion, NAD+ (nicotinamide-adenine dinucleotide) levels were assessed, and the tissues were examined immunohistochemically for oxidative stress and apoptosis.During reperfusion, the 3-AB(+) group showed significantly higher (P=0.005)dp/dt and lower creatine phosphokinase (CPK) level and glucotamic-oxaloacetic transaminase (GOT) in the effluent (CPK ; P=0.003 GOT ; P<0.001) The cardiomyocytes of the 3-AB(+) group also preserved a higher NAD+ level (P<0.001). Immunohistochemical study of oxidative stress revealed a lesser extent (P=0.007) of nuclear staining and a lower fraction of apoptosis in the 3-AB(+) group.In conclusion, cardioplegic solution supplemented with PARS inhibitor provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress.

甚至在当前心脏手术中，缺血性重新灌注损伤也是最严重的问题之一。已经建议聚（腺苷5'-二磷酸核糖）合成酶（PARS）抑制剂通过防止与氧化应激相关的能量耗竭来减轻缺血 - 再灌注损伤。我们研究的目的是评估含有PARS抑制剂3-氨基苯甲酰胺（3-AB）的心倍左右溶液的疗效，以防止心肌抑制引起的缺血 - 替进性损伤。由心骨抑制引起的溶解大鼠的心脏。溶解的大鼠心脏置于langendorff Appus and Perfused。用心脏地唇溶液（圣托马斯溶液）以30分钟的时间间隔将心脏捕获90分钟，然后再填充20分钟。 3-AB（ - ）组（n = 8）中大鼠的心脏用标准的心骨溶液和末端温暖的心脏杂质灌注，而3-AB（+）组（n = 8）收到了这些溶液，这些溶液补充了3-AB（100 microm）。左心室功能和心脏释放前后的心脏酶的释放受到监测。再灌注后，评估了NAD+（烟酰胺 - 腺嘌呤二核苷酸）水平，并检查了组织在免疫化学上的氧化应激和凋亡中的免疫化学化学作用。进行再灌注，3-AB（+）组显示出明显更高（p = 0.005）DP/DT和下肌酸磷酸化酶（P = 0.005） - （GOT）在废水中（CPK; P = 0.003 GET; P <0.001）3-AB（+）组的心肌细胞也保留了更高的NAD+水平（P <0.001）。氧化应激的免疫组织化学研究表明，在3-AB（+）组中，核染色的程度较小（P = 0.007），降低了凋亡的较低程度。结论，通过抑制剂的心脏胡毛溶液补充了抑制剂的心骨溶液，可通过抑制性氧化应力有效地抑制了心脏脑性缺血性氧化应力。