不同浓度脂联素通过减轻氧化应激损伤保护缺血再灌注心肌

Protective Effect of Different Concentrations of Adiponectin on Ischemia Reperfusion Myocardium by Relieve Oxidative Stress

目的观察不同浓度脂联素对大鼠心肌缺血再灌注损伤及其所引起的氧化应激的影响,以探讨脂联素保护缺血再灌注心肌是否与减轻氧化应激有关。方法将80只健康SD大鼠随机分成假手术组、缺血再灌注组、低浓度脂联素组(60 ng/g)、中浓度脂联素组(120 ng/g)和高浓度脂联素组(180 ng/g),每组16只。假手术组只穿线,不结扎,旷置225 m in;缺血再灌注组冠状动脉前降支结扎45 m in后,再灌注180 m in;各脂联素组于缺血前30m in经股静脉给予不同浓度脂联素,再进行缺血再灌注。各组进一步随机分为两个亚组。亚组1(8只)在缺血45m in再灌注180 m in后,用Evans b lue-TTC双染法测定心肌梗死面积;亚组2(8只)在大鼠再灌注180 m in后对左心室内压及单位时间左心室内压变化值(±dp/dt)等血流动力学指标进行检测。实验结束后,在心尖处取血并取心肌组织,测定大鼠血清超氧化物歧化酶活性、心肌组织总一氧化氮合酶及一氧化氮含量。结果与假手术组比较,缺血再灌注组大鼠血清中超氧化物歧化酶活性及心肌组织中总一氧化氮合酶和一氧化氮含量明显下降,心肌梗死面积增大;与缺血再灌注组比较,各浓度脂联素组心肌梗死面积减小,心肌舒缩功能有所改善,大鼠血清超氧化物歧化酶活性及心肌组织总一氧化氮合酶和一氧化氮含量显著增加,并随脂联素浓度增加而增加。结论脂联素对缺血再灌注心肌细胞有保护作用,减少缺血再灌注心肌的梗死面积,改善心脏舒缩功能;其作用机制可能是通过增加缺血再灌注心肌组织总一氧化氮合酶和一氧化氮含量及血清超氧化物歧化酶活性,从而减轻氧化应激损伤。

Aim To investigate the effect of different concentrations of adiponectin on ischemia-reperfusion myocardium and oxidative stress in rats,and their dose-effect relationship. Methods Eighty healthy Sprague-Dawley rats were randomly divided into five groups： sham-operated group,ischemia-reperfusion group（I/R）,low,middle and high concentrations of adiponectin（60,120,180 ng/g） group,with 16 rats for each group.Sham group were suffered with sham operation.I/R group were undergone the left anterior descending branch of coronary artery ischemia for 45 min and reperfused for 180 min fusion.Rats in different adiponectin groups were infused with adiponectin for 30 min before ischemia-reperfusion.Then the rats in each group were then randomly divided into two sub-groups,eight rats in sub-group 1 and eight in sub-group 2.After reperfusion,the infarct size was determined by using Evans blue and TTC double dye staining in sub-group 1.In group 2 the left ventricular developed pressure（LVDP）,±dp/dtmax were recorded at the end of reperfusion.At the end of experiment,the activities of total nitric oxide synthase（tNOS） and nitric oxide（NO）in the myocardium and superoxide dismutase（SOD） activity of serum were examined. Results Compared with sham-operated group,the level of tNOS and NO in the myocardium and serum SOD was downregulated in I/R group,whereas the cardiac infarct size was increased.The infarct size was reduced in different adiponectin groups compared with I/R group,while the levels of SOD,tNOS and NO were significantly increased with a dose-dependent improvement of ischemia/reperfusion-induced myocardial,contractile dysfunction was improved dose-dependently. Conclusion Adiponecin may protect hearts from ischemia-reperfusion injury in rats by reducing cardiac infarct size and improving myocardial contractile dysfunction.The molecular mechanism may involve preservation of tNOS,NO and SOD in serum and myocardial tissue,and protect myocardium from ischemia-reperfusion-induced oxidative stress.