Besse S, Bulteau A L, Boucher F, Riou B, Swynghedauw B, de Leiris J
Laboratoire Croissance cellulaire, Réparation et Régénération Tissulaires, Université Paris 12 - Val da Marne, Créteil, France.
J Physiol Pharmacol. 2006 Dec;57(4):541-52.
Cardiovascular ageing is associated with an increase in cardiac susceptibility to ischaemia and reperfusion and production of reactive oxygen species has been suspected to be responsible for this age-associated particular vulnerability. To determine whether administration of antioxidant treatment could afford some protection against ischaemia and reperfusion during aging, isolated perfused hearts from adult and senescent rats were submitted to normoxia (180 min), prolonged low-flow ischaemia (15% of initial coronary flow;180 min) or low-flow ischaemia/reperfusion (45 min/30 min), without or with antioxidant enzymes (superoxide dismutase+catalase; 50IU/ml). Contractile function and coronary perfusion were measured and protein oxidation was quantitated in left ventricle after normoxia, ischaemia and ischaemia/reperfusion. Protein oxidation was higher in senescent than in adult hearts after ischaemia-reperfusion, in contrast to prolonged ischaemia. During prolonged ischaemia, antioxidant treatment prevented coronary vasoconstriction at both ages and delayed contractile dysfunction in senescent hearts but did not limit protein oxidation. During reperfusion, antioxidant treatment prevented coronary vasoconstriction and protein oxidation at both ages and considerably improved recovery of contractile function in senescent hearts. In conclusion, antioxidant treatment fully protects the senescent heart against ischaemia/reperfusion but not against prolonged ischaemia injury, indicating that oxidative stress plays a central role in the age-associated vulnerability to ischaemia-reperfusion.
心血管衰老与心脏对缺血再灌注的易感性增加有关,活性氧的产生被怀疑是导致这种与年龄相关的特殊易损性的原因。为了确定给予抗氧化治疗是否能在衰老过程中为缺血再灌注提供一定的保护,将成年和老年大鼠的离体灌注心脏置于常氧(180分钟)、长时间低流量缺血(初始冠状动脉流量的15%;180分钟)或低流量缺血/再灌注(45分钟/30分钟)条件下,分别给予或不给予抗氧化酶(超氧化物歧化酶+过氧化氢酶;50IU/ml)。测量收缩功能和冠状动脉灌注,并对常氧、缺血和缺血/再灌注后左心室的蛋白质氧化进行定量。与长时间缺血相反,缺血再灌注后老年心脏的蛋白质氧化高于成年心脏。在长时间缺血期间,抗氧化治疗在两个年龄段均能防止冠状动脉收缩,并延缓老年心脏的收缩功能障碍,但不能限制蛋白质氧化。在再灌注期间,抗氧化治疗在两个年龄段均能防止冠状动脉收缩和蛋白质氧化,并显著改善老年心脏收缩功能的恢复。总之,抗氧化治疗能使老年心脏完全免受缺血/再灌注损伤,但不能防止长时间缺血损伤,这表明氧化应激在与年龄相关的缺血再灌注易损性中起核心作用。