Abstract:

Objective To explore the protective effect of nicorandil  postconditioning on myocardium of rats with  myocardial ischemia -reperfusion  injury(MIRI) in rats and to discuss its mechanism.Methods 26 SD rats were divided into control group(n=8)， isoproterenol(ISO) group(n=8) and nicorandil postconditioning group(n=10).The rats in ISO group  were injected intraperitoneally with isoproterenol (5 mg/kg）at an interval of 24 h for 3 d; the rats in control group only received an injection of same amount of saline;the  rats in nicorandil postconditioning group were injected intravenously with nicorandil (1 mg/kg) 1 h after ISO injection  once a day, lasting for 3 d.The rats were killed 24 h after the third injection of ISO.The activities of serum creatine kinase （CK） and lactate dehydrogenase （LDH） of  rats in various groups  were detected;the histopathological changes of myocardium of rats in various groups were observed  by routine HE staining;the expressions of Caspase-3 protein were determined by immunohistochemistry;the apoptosis of cardiocytes of rats in various groups was analyzed by TUNEL staining.Results There were no significant differences in the activites of serum CK and LDH between   nicorandil postconditioning group and control group（P>0.05）， but the activities of CK and LDH in control and nicorandil postconditioning groups were lower than those in  ISO group （P<0.05）.The HE staining results showed local degeneration,necrosis and inflammation in ISO group,but slightly necrosis and inflammation in nicorandil postconditioning group and no pathological changes  in control group.Immunohistochemistry staining showed that Caspase-3 was positive in cardiocyte plasma in ISO group; however， there were no Caspase-3 expression in control and nicorandil postconditioning groups.The apoptosis index（AI）  in nicorandil postconditioning group was significantly decreased compared with ISO group（P<0.01）.Conclusion Nicorandil can attenuate MIRI of rats，and its mechanism may be related to inhibiting Caspase-3 pathway and decreasing the cardiocyte apoptosis.