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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35min,持续再灌注12h;(2)IPoC组,缺血35min后,先给予20s再灌注后再缺血20s,共3次循环,然后持续再灌注12h;(3)MT组,在持续再灌注前10min静脉注入米诺环素45mg/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。
Objective To observe the effects of IPoC and MT on myocardial ischemia-reperfusion (I / R) in rabbits with atherosclerosis (AS) and determine whether minocycline is suitable as a medicine Post-processing play a cardioprotective role. Methods The rabbits were randomly divided into 3 groups: (1) I / R group, myocardial ischemia for 35min, continuous reperfusion for 12h; (2) IPoC After ischemia for 35 min, the rats were reperfused for 20 s followed by ischemia for 20 s for a total of 3 cycles and then reperfused for 12 h. (3) In the MT group, minocycline 45 mg / kg . The contents of serum lipids, malondialdehyde (MDA), soluble intercellular adhesion molecule (sICAM) and cardiac troponin T (cTnT) were measured by biochemical methods. The levels of superoxide dismutase (SOD) and myeloperoxidase )active. The myocardial infarct size (IS) and apoptosis index (AI) were measured by pathology. The expression of bcl-2 and caspase-3 in myocardium was detected by RT-PCR. Results Compared with the I / R group, the ISCs in the IPoC group and the MT group decreased significantly, while the levels of plasma MDA, sICAM and cTnT were significantly decreased, the activity of MPO decreased and the activity of SOD increased significantly (P <0.05) The expression of caspase-3 decreased and the expression of bcl-2 increased (all P <0.05). Conclusion IPoC and MT can protect myocardium from ischemia-reperfusion injury in AS rabbits, which is related to their anti-oxidation, anti-inflammation, up-regulation of bcl-2 and down-regulation of caspase-3. Minocycline acts as an effective aftertreatment drug to protect the heart.