Background and Objective: Myocardial Ischemia-Reperfusion Injury (MIRI) results in damage to heart structure and dysfunction, which seriously threatens life safety. To explore the role of nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in morphine preconditioning to alleviate MIRI in rats with doxorubicin hydrochloride-induced heart failure (HF). Materials and Methods: HF model was established by tail vein injection of doxorubicin hydrochloride. Then model rats were randomly divided into sham operation (sham), ischemia-reperfusion (model), morphine preconditioning (MFC), oleanolic acid derivative 85 (OAD-85) +morphine preconditioning (MOA) and OAD-85 control (OAD) groups. Myocardial infarction, changes in histopathology and ultrastructure, reactive oxygen species (ROS) level, oxidative stress, apoptosis rate and protein expressions of Nrf2 and Heme Oxygenase-1 (HO-1) were detected by triphenyl tetrazolium chloride staining, hematoxylin-eosin staining, transmission electron microscopy, 2',7'-dichlorodihydrofluorescein diacetate staining, TUNEL staining and western blotting, respectively. Results: Compared with the model group, myocardial infarction proportion, ROS, malondialdehyde (MDA) and apoptosis rate significantly reduced in the MFC group, whereas superoxide dismutase (SOD) activity and expressions of Nrf2 and HO-1 increased. Compared with the MFC group, the MOA group exhibited increased myocardial infarction proportion, ROS, MDA and apoptosis rate as well as decreased activity of SOD and expressions of Nrf2 and HO-1. Compared with the model, MFC and MOA groups, myocardial infarction proportion, ROS, MDA and apoptosis rate rose significantly, while SOD activity and expressions of Nrf2 and HO-1 decreased significantly in the OAD group. Conclusion: The Nrf2/ARE pathway is involved in morphine preconditioning to alleviate MIRI in rats with HF induced by doxorubicin hydrochloride. Morphine can markedly activate the Nrf2/ARE pathway to play an antioxidant role.
Shirong Luo, Yu Fang and Jinhua Wang, 2022. Role of Nrf2/ARE Pathway in Morphine Preconditioning to Alleviate Rat Myocardial Ischemia-Reperfusion Injury. International Journal of Pharmacology, 18: 1116-1125.