米诺环素和缺血后处理对动脉粥样硬化兔心肌缺血再灌注的影响

目的 观察缺血后处理(IPoC)和米诺环素后处理(MT)对动脉粥样硬化(AS)兔心肌缺血再灌注(I/R)的影响,确定米诺环素是否适合作为药物后处理发挥心脏保护作用.方法 注入异种血清白蛋白免疫损伤血管内膜后高脂饲料喂养6周,复制AS兔,随机分成3组,(1)I/R组,心肌缺血35 min,持续再灌注12 h;(2)IPoC组,缺血35 min后,先给予20 s再灌注后再缺血20 s,共3次循环,然后持续再灌注12 h;(3)MT组,在持续再灌注前10 min静脉注入米诺环素45 mg/kg.生化法测量血脂、丙二醛(MDA)、可溶性细胞间黏附分子(sICAM)和心肌钙蛋白T(cTnT)含量;生化法测量血清中超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)活性.病理学方法测量心肌梗死范围(IS)和凋亡指数(AI);RT-PCR检测心肌组织bcl-2和caspase-3的表达量;组织形态学验证兔AS模型.结果 与I/R组相比,IPoC组和MT组兔心肌IS显著降低,血浆MDA、sICAM、cTnT水平显著降低、MPO活性降低、SOD活力明显增加(P均<0.05);心肌AI明显降低,caspase-3表达量减少,bcl-2表达量增加(P均<0.05).结论 IPoC和MT对AS兔缺血再灌注的心肌有保护作用,与其抗氧化、抗炎、上调bcl-2、下调caspase-3有关.米诺环素可以作为有效的后处理药物发挥保护心脏的作用.

The effect of minocydine and ischemic postconditioning on myocardial ischemia-reperfusion of atherosderosis rabbits

Objective To determine whether minocycline could reduce myocardial ischemia-reperfusion injury as a postconditioning drugs through comparing the effect of minocycline postconditioning （MT） and ischemic postconditioning（IPoC） on myocardial ischemia-repeffusion in atherosclerosis （AS）rabbits. Methods 40 male healthy rabbits were injected with beef serum albumin following feeding with high fat diet for 6 weeks to make AS model. AS rabbits were randoml）; divided into; 3 groups, （ 1 ） I/n group, myocardial ischemia for 35 rain, then sustained reperfusion for 12 h;（2） IPoC group,ischemia for 35 rain,then reperfusion for 20 s and ischemia for 20 s, a total of 3 cycles, and then sustained reperfusion for 12 h; （3） MT group,intravenous injection of minocycline 10 rain before sustained reperfusion. Serum MDA, sICAM and cTnT level were detected by biochemical methods. Serum enzymatic activity of SOD and MPO were detected. The myocardial infarct size （IS） and apoptosis index （A!） were analyzed. The expression of bcl-2 and caspase-3 mRNA were measured by RT-PCR. The morphological changes in myocardial tissue were evaluated to verify the AS model. Results Compared with lfR group, the myocardial IS, the plasma MDA, sICAM, MPO and cTnT level, the enzymatic activity of MPO in the rabbits of IPoC group and the MT group were significantly decreased respectively, whereas plasma SOD activity were increased （P all 〈 0. 05 ）. The myocardial AI and easpase-3 mRNA expression in the rabbits of IPoC group and the MT group Were lower than those in the rabbits of I/R group, and bcl-2 mRNA expression was higher than that in the rabbits of I/R group （ P all 〈 0. 05）. Condusions The ischemic postconditioning and minocycline postconditioning could effectively reduce ischemia-reperfusion injury in the atherosclerosis rabbits, and the mechanisms involving the anti-oxidant effect, antiinflammatory effect, up-regulation bcl-2 expression, and down-regulation caspase-3 expression. Minocycline could be used as an effective pharmacologic postconditioning drug to protect the cardiac injury.