| Objective: To investigate the protective effects and mechanisms of nicorandil on Nrf2/HO-1 signaling pathway in prevention of myocardial injury after coronary microembolization in rats.Methods: Sixty adult SD rats were randomized to sham operated group(Sham group),coronary microembolization group(CME group),CME plus nicorandil group(CME+NIC group)and Gavage control group,fifteen rats in each group.The 42 μm microspheres were injected into the left ventricle to establish the coronary microembolization model in rats of the CME group and CME+NIC group and Gavage control group.For rats in the sham group,using the same methods and the same dose of normal saline was substituted for microspheres.Rats in the CME+NIC group received nicorandil 3 mg/(kg·d)for 7 days before the operation.The cardiac function was assessed by echocardiography,The mRNA expression levels of Nrf2 、 HO-1 in the myocardial tissues were detected by RT-PCR and The protein expression levels of Nrf2、HO-1,Bcl-2,Bax and cleaved caspase-3 in the myocardial tissues were detected by Western blot at 6 h after operation.The size of the microinfarction area was measured by hematoxylin-eosin and hematoxylin-basic fuchsin-picric acid(HBFP).Cardiomyocyte apoptosis was detected by TUNEL staining.Results: Compared with the sham group,the cardiac function,the expression level of Nrf2,HO-1 and Bcl-2were decreased while myocardial apoptosis and the expression of Bax and cleaved caspase-3 were increased in the CME group,CME+NIC group and Gavage control group(P<0.05).Compared with the CME group,cardiac function was significantly improved,the expression levels of Nrf2,HO-1,and Bcl-2 were increased,while the expression of Bax and cleaved caspase-3 were decreased,and the myocardial apoptosis was attenuated in the CME+NIC group(P<0.05).The cardiomyocyte apoptosis rate,the cardiac function,the expression level of Nrf2、HO-1、Bcl-2、Bax、cleaved Caspase-3 have no significant difference between the CME group and Gavage control group(P>0.05).Interestingly,there was no significant difference(P>0.05)in myocardial infarct size among groups.Conclusion: Nicorandil pretreatment inhibits myocardial apoptosis and improves cardiac function after coronary microembolization,the potential protective mechanisms may activation of Nrf2/HO-1 signaling pathway in rats... |
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