| Objective:The incidence of ischemic heart disease increased year by year, how to protect myocardial ischemia injury is the focus of current research. Proved by the experiment that myocardial ischemic preconditioning and ischemic postconditioning are successful methods, have been shown to reduce ischemia reperfusion arrhythmia, reduce necrosis. But due to ischemic preconditioning need to intervene before ischemia, which requires predict myocardial ischemia occurred at a time, and the need for complex invasive operations to implement local ischemia, so limits its development in clinic; Ischemic postconditioning may not need to predict ischemic time, but still depends on complex invasive operation to complete. so this approach is limited. The research on ischemic preconditioning and ischemic postconditioning are limited to basic research level.Activation of mitochondrial KATP channel has been suggested in several studies as a principle mechanism of ischemic preconditioning. This has lead to the hypothesis that drugs that open mitochondrial KATP channel can mimic preconditioning and postconditioning (pharmacological preconditioning and pharmacological postconditioning).Previous studies about the cardioprotective effects of nicorandil preconditioning have concentrated on the assessment of infarct size reduction. However, little attentions have been paid for investigating the cardioprotective effects of these drugs against ischemia/reperfusioninduced hemodynamic, biochemical and histological changes. The aim of the present study was directed to investigate the protective effects of nicorandil postconditioning on these changes associated with myocardial ischemia injury. Nicorandil has been reported to induce the cardioprotection by opening the mitochondrial KATP channels of the myocardiocytes. Up to now the mechanism of cardioprotection is not fully understood. The purpose of this study is to study the effect of nicorandil postconditioning on myocardial ischemic injury and its mechanism of action from the biochemical and histological changes. The rates were injected intraperitoneally with low dose isoproterenol to induce model of myocardial ischemic injury, laid the foundation for future research; This study in order to protect the mitochondria as the breakthrough point, use pharmacological postconditioning simulated ischemic postconditioning, achieved good results, provides a new idea for the symptomatic treatment of clinical myocardial ischemia and hypoxia, and has very important realistic significance.Methods:30SD rats were divided into control group, isoproterenol group and nicorandil postconditioning group. Rats in ISO group were injected intraperitoneally with isoproterenol (5mg·kg-1) at an interval of24h for3days; Rats in control group only receied an injection of same amount of saline; Rats in nicorandil(lmg·kg-1) postconditioning group were injected intravenous1h after ISO injection for once perday lasting for3d. Cardiac injury enzyme creatine kinase (CK),lactate dehydrogenase (LDH) and cardiac troponine I (cTnI) for rats serum were evaluated before killing the rats. Histopathological changes were evaluated by routine HE staining and Caspase-3protein were determined by immunocytochemistry. Apoptosis was analyzed by TUNEL staining. Histopathological changes were evaluated by Kir6.2and VDAC immumofluorescence staining and Nitrotyrosine immunohistochemistry staining. Kir6.2expression was further detected by western blot.I1-10expression was analyzed by PCR.Results:There are no significant difference in the levels of serum CK and LDH of rats in chontrol and nicorandil postconditioning group (P＞0.05), The levelsof CK and LDH were lower in control and nicorandil postconditioning group compared with ISO group (P＜0.05). Isoproterenol-induced rats showed significant increase in the levels of serum cTnI, which was decreased by Nicorandil (P＜0.01). HE staining showed local degeneratin,necrosis and inflammation in ISO group,but slightly necrosis and inflammation in nicorandil group. No pathological changes were detected in control group.Immunohistochemistry staining showed that Caspase-3were positive in cardiocytes cytoplasm; however, all of the detrimental effects of large amount of ISO were attenuated by Nicorandil. The apoptosis indexes (AI) significantly decreased in nicorandil postconditioning group compared with ISO group (P＜0.01). Immunofluorescence staining showed that Kir6.2was increased in Nicorandil group, but decreased in ISO group. These results were further confirmed by Kir6.2Western Blot. However, in ISO treated rats, Nitrotyrosine was positive in cardiocytes cytoplasm, which were negative in Nicorandil and control groups. Furthermore, IL-10mRNA expression was increased in Nicorandil group compared with that in ISO group.Conclusion:1. The rates were injected intraperitoneally with low dose isoproterenol (5mg·kg-1) can induce model of myocardial ischemic injury.2. Nicorandil pharmacological postconditioning has obvious protective effect on myocardial ischemia injury.3. Nicorandil attenuates myocardial ischemia injury in the rats, and its meachanism maybe related with inhibiting oxidative stress generation and inflammatory response via opening opening of the mitochondrial KATP channel, inhibiting myocardial apoptosis and inflammatory reaction. |
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