Bowes J, Ruetten H, Martorana P A, Stockhausen H, Thiemermann C
The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, UK.
Eur J Pharmacol. 1998 Oct 23;359(2-3):143-50. doi: 10.1016/s0014-2999(98)00638-4.
The effect of the Poly (adenosine 5'-diphosphate ribose) synthetase (PARS) inhibitor 3-aminobenzamide on (i) infarct size caused by regional myocardial ischaemia (60 min) and reperfusion (3 h) in the anaesthetised pig, and (ii) on the cell injury/necrosis of human cardiomyoblasts caused by hydrogen peroxide (3 mM) was investigated. Regional myocardial ischaemia and reperfusion resulted in an infarct size of 66+/-3% of the area at risk, which was reduced by 3-aminobenzamide (to 44+/-2%, n=6), but not 3-aminobenzoic acid (66+/-5%, n=4). 3-aminobenzamide also reduced the postischaemic contractile dysfunction. 3-aminobenzamide, but not 3-aminobenzoic acid, abolished the increase in PARS activity as well as the cell injury/necrosis caused by hydrogen peroxide in the cardiomyoblasts. In conclusion, the PARS inhibitor 3-aminobenzamide reduces myocardial reperfusion injury in the pig, and attenuates the cell injury and death associated with oxidant stress in human cardiomyoblasts. We propose that the activation of PARS plays an important role in the injury associated with oxidant stress of the heart.
研究了聚（腺苷5'-二磷酸核糖）合成酶（PARS）抑制剂3-氨基苯甲酰胺对以下两方面的影响：（i）麻醉猪局部心肌缺血（60分钟）和再灌注（3小时）所致的梗死面积；（ii）过氧化氢（3 mM）所致的人成心肌细胞的细胞损伤/坏死。局部心肌缺血和再灌注导致梗死面积占危险区域面积的66±3%，3-氨基苯甲酰胺可使其减小（降至44±2%，n = 6），但3-氨基苯甲酸则无此作用（66±5%，n = 4）。3-氨基苯甲酰胺还减轻了缺血后的收缩功能障碍。3-氨基苯甲酰胺而非3-氨基苯甲酸消除了过氧化氢所致的成心肌细胞中PARS活性增加以及细胞损伤/坏死。总之，PARS抑制剂3-氨基苯甲酰胺可减轻猪的心肌再灌注损伤，并减轻人成心肌细胞中与氧化应激相关的细胞损伤和死亡。我们认为，PARS的激活在心脏氧化应激相关损伤中起重要作用。
