Abstract: Objective　To investigate the role of the nuclear factor E2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway in reduction of myocardial ischemia-reperfusion injury (MIRI) by morphine preconditioning in rats with heart failure induced by doxorubicin hydrochloride.　Methods　The HF model rats were randomly divided into the following 5 groups: a sham group, a model group, a MFC group, a MOA group and an OAD group. The normal group was set at the same time. The HF model rats were ligated at the anterior descending branch of the left coronary artery for 30 minutes and then were perfused for 120 minutes to construct the MIRI model. The MFC group rats were pretreated with morphine before operation. The OAD group rats were pretreated with Nrf2/ARE signaling pathway inhibitor before operation, the MOA group with Nrf2/ARE signaling pathway inhibitor plus morphine.  TUNEL was used to detect the apoptosis rate. Western blot was used to detect the expressions of Nrf2 and HO-1.　Results Compared with the normal group, the apoptosis rate and the expressions of Nrf2 and HO-1 in the model group significantly increased. Compared with the model group, the apoptosis rate of the MFC group significantly reduced, and the expressions of Nrf2 and HO-1 significantly increased. Compared with the MFC group, the apoptosis rate of the MOA group significantly increased, and the expressions of Nrf2 and HO-1 significantly reduced. Compared with the model group, the apoptosis rate of the OAD group significantly increased, and the expressions of Nrf2 and HO-1 significantly increased. There were statistical differences in the expressions of Nrf2, HO-1 and the apoptosis rate among the groups (P<0.05).　Conclusions　In the MIRI rat model induced by HF, morphine preconditioning can obviously activate the Nrf2/ARE pathway and inhibit cell apoptosis.

Key words: Heart failure;　Doxorubicin hydrochloride;　Myocardial ischemia-reperfusion injury, Nrf2/ARE signaling pathway