Huang Conggang, Li Rui, Zeng Qiutang, Ding Yanping, Zou Yongguang, Mao Xiaobo, Hu Wei, Xiong Rong, Li Ming
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Cardiology, The Central Hospital of Xiaogan, Xiaogan, 432100, China.
J Huazhong Univ Sci Technolog Med Sci. 2012 Aug;32(4):524-529. doi: 10.1007/s11596-012-0090-y. Epub 2012 Aug 11.
This study examined the protective effect of ischemic postconditioning (IPoC) and minocycline postconditioning (MT) on myocardial ischemia-reperfusion (I/R) injury in atherosclerosis (AS) animals and the possible mechanism. Forty male healthy rabbits were injected with bovine serum albumin following feeding on a high fat diet for 6 weeks to establish AS model. AS rabbits were randomly divided into 3 groups: (1) I/R group, the rabbits were subjected to myocardial ischemia for 35 min and then reperfusion for 12 h; (2) IPoC group, the myocardial ischemia lasted for 35 min, and then reperfusion for 20 s and ischemia for 20 s [a total of 3 cycles (R20s/I20s×3)], and then reperfusion was sustained for 12 h; (3) MT group, minocycline was intravenously injected 10 min before reperfusion. The blood lipids, malondialdehyde (MDA), superoxide dismutase (SOD), soluble cell adhesion molecule (sICAM), myeloperoxidase (MPO), and cardiac troponin T (cTnT) were biochemically determined. The myocardial infarction size (IS) and apoptosis index (AI) were measured by pathological examination. The expression of bcl-2 and caspase-3 was detected in the myocardial tissue by using reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the AS models were successfully established. The myocardial IS, the plasma levels of MDA, sICAM, MPO and cTnT, and the enzymatic activity of MPO were significantly decreased, and the plasma SOD activity was significantly increased in IPoC group and MT group as compared with I/R group (P<0.05 for all). The myocardial AI and the caspase-3 mRNA expression were lower and the bcl-2 mRNA expression was higher in IPoC and MT groups than those in I/R group (all P<0.05). It is concluded that the IPoC and MT can effectively reduce the I/R injury in the AS rabbits, and the mechanisms involved anti-oxidation, anti-inflammation, up-regulation of bcl-2 expression and down-regulation of caspase-3 expression. Minocycline can be used as an effective pharmacologic postconditioning drug to protect myocardia from I/R injury.
本研究探讨了缺血后处理（IPoC）和米诺环素后处理（MT）对动脉粥样硬化（AS）动物心肌缺血再灌注（I/R）损伤的保护作用及其可能机制。40只健康雄性兔高脂饮食喂养6周后注射牛血清白蛋白以建立AS模型。将AS兔随机分为3组：（1）I/R组，兔心肌缺血35分钟，然后再灌注12小时；（2）IPoC组，心肌缺血持续35分钟，然后再灌注20秒、缺血20秒[共3个循环（R20s/I20s×3）]，然后持续再灌注12小时；（3）MT组，再灌注前10分钟静脉注射米诺环素。生化检测血脂、丙二醛（MDA）、超氧化物歧化酶（SOD）、可溶性细胞间黏附分子（sICAM）、髓过氧化物酶（MPO）和心肌肌钙蛋白T（cTnT）。通过病理检查测量心肌梗死面积（IS）和凋亡指数（AI）。采用逆转录-聚合酶链反应（RT-PCR）检测心肌组织中bcl-2和caspase-3的表达。结果显示成功建立了AS模型。与I/R组相比，IPoC组和MT组心肌IS、血浆MDA、sICAM、MPO和cTnT水平以及MPO酶活性显著降低，血浆SOD活性显著升高（均P<0.05）。IPoC组和MT组心肌AI和caspase-3 mRNA表达低于I/R组，bcl-2 mRNA表达高于I/R组（均P<0.05）。结论：IPoC和MT可有效减轻AS兔的I/R损伤，其机制涉及抗氧化、抗炎、上调bcl-2表达和下调caspase-3表达。米诺环素可作为一种有效的药物后处理药物保护心肌免受I/R损伤。
