Cannabinoid Receptor-2 agonist AM1241 Attenuates Myocardial Ischemia-Reperfusion-Induced Oxidative Stress in Rats via Nrf2/HO-1 Pathway.

Objective: The cannabinoid receptor-2 agonist AM1241 exhibits notable cardioprotective effects against myocardial infarction, positioning it as a promising therapeutic candidate for cardiovascular disease. This study explores AM1241's protective role in myocardial ischemia-reperfusion (IR) injury and its association with the Nrf2/HO-1 pathway.

Methods: In an established Sprague-Dawley rat IR model, AM1241's impact on cardiac injury was assessed through echocardiography, 2,3,5-triphenyl tetrazolium chloride staining, and histological analysis. H9c2 cells underwent hypoxia-reoxygenation, with AM1241's influence on cell viability determined by the CCK-8 assay. Reactive oxygen species (ROS) production was measured using the DCFH-DA assay, and Nrf2 and HO-1 protein expressions were evaluated through immunofluorescence and Western blot.

Results: Myocardial ischemia-reperfusion injury (MIRI) increased infarct size, inflammatory cell presence, oxidative and nitrosative stress, impaired cardiac function, and elevated apoptosis rates. AM1241 mitigated these effects, enhancing cell viability, reducing ROS production, and upregulating Nrf2 and HO-1 expression. The antioxidant effect of AM1241 was inhibited by ML385 intervention.

Conclusions: AM1241 attenuates oxidative stress, alleviates MIRI, and activates the Nrf2/HO-1 signaling pathway, underscoring its potential as a therapeutic strategy for MIRI.