目的观察强力霉素预处理对在体大鼠心肌缺血/再灌注(I/R)损伤时基质金属蛋白酶-1(MMP-1)和MMP-9表达的影响。方法64只体重300-350g的健康雄性SD大鼠被随机分为假手术组(n=16)、I/R组(n=24)和强力霉素预处理组(n=24)。分别观察在体大鼠心肌缺血60min再灌注120min后的心肌I/R损伤,以及强力霉素预处理对其心功能、血浆肌酸激酶(CK)和乳酸脱氢酶(LDH)水平及心肌组织髓过氧化物酶(MPO)活性的影响;以免疫组化法检测心肌细胞MMP-1和MMP-9的蛋白表达。结果心肌再灌注120min时,I/R组左室收缩压(LVSP)、左室压最大上升和下降速率(±dp/dtmax)均较假手术组显著下降,左室舒张末压(LVEDP)、血浆CK和LDH以及心肌组织MPO活性均显著升高,且MMP-1和MMP-9的蛋白表达明显增强(P〈0.05或P〈0.01)。而强力霉素预处理组心功能各项指标以及血浆CK、LDH均明显改善,MMP-1和MMP-9的蛋白表达均明显受抑,与I/R组比较差异均有统计学意义(P〈0.05或P〈0.01)。结论强力霉素预处理在减轻在体大鼠心肌I/R损伤的同时,还可抑制MMP-1和MMP-9的蛋白表达。
Objective To investigate the effects of preconditioning with doxycyeline on ischemia/reperfusion (I/R) injury and expressions of matrix metalloproteinase-1 (MMP-1) and MMP-9 in myocardium in rat in vivo. Methods Sixty-four healthy male SD rats, weighing 300-350 g, were randomly devided into three groups: sham operation group (n=16), I/R group (n=24), and doxycycline preconditioning group (n=24). The heart function, plasma level of creatine kinase (CK) and lactate dehydrogenase (LDH), and the activity of myeloperoxidase (MPO) were respectively determined in rat myocardium after ischemia for 60 minutes and reperfusion for 120 minutes or with the same procedure but with precondition of Doxycycline. Also the expressions of MMP-1 and MMP-9 was determined by immunohistochemistry. Results In I/R group, left ventricular systolic pressure (LVSP) and the maximun and minimum first derivative of LVSP (±dp/dtmax) were significantly less, and left ventricular enddiastolic pressure (LVEDP), CK, LDH, the activity of MPO, and the protein expressions of MMP-1 and MMP-9 were remarkably higher compared with the sham operation group (P〈0.05 or P〈0.01). Heart function was improved, CK, LDH, MPO and the expressions of MMP-1 and MMP-9 were reduced obviously by doxycycline preconditioning compared with the I/R group (P〈0.05 or P〈0.01). Conclusion Precondition with doxycycline could remarkably abate I/R injury of rat myocardium in vivo and inhibit the expressions of MMP-1 and MMP-9.