Hirudin protects against isoproternol-induced myocardial infraction by alleviating oxidative via an Nrf2 dependent manner.

Oxidative stress plays a critical role in the progression of myocardial injury. Increasing evidence suggests that hiruidin can treat patients with cardio-injury. However, the mechanism of hirudin against myocardial infraction remains unknown. In the present study, we evaluated the potential role and mechanism of hirudin on both isoproterenol (ISO)-induced myocardial infraction (MI) in rats and Hypoxia-Reoxygenation model in H9C2 cells. Compared with the model group, hirudin apparently decreased the levels of myocardial Creatine Kinase Isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), and alleviated myocardial histopathological changes induced by ISO injection. The underlying mechanisms were revealed by the following observations: Hirudin exerted its cardioprotective effect via restoring super oxide dismutase (SOD), attenuating reactive oxygen species (ROS) and malondialdehyde (MDA). It induced the activation of Nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway through disrupting Keap1-Nrf2 complex, thus Nrf2 translocated from cytoplasm to nucleus to regulate Nrf2-dependent gene (HO-1, SOD) expressions. Furthermore, it should be noted that hirudin restored mitochondrial membrane potential in addition to cytochrome C-related apoptosis.