{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T16:58:12Z","timestamp":1784221092407,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":211,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874403"],"award-info":[{"award-number":["81874403"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p><jats:italic>Objectives<\/jats:italic>. We aimed to observe the protective effect of <jats:italic>\u03ba<\/jats:italic> opioid receptor (<jats:italic>\u03ba<\/jats:italic>\u2010OR) agonist on myocardial injury in heart failure (HF) rats and its effect on Ca<jats:sup>2+<\/jats:sup>\u2010SERCA2a and to explore the regulatory mechanism with the Nrf2\/HO\u20101 signaling pathway. <jats:italic>Methods<\/jats:italic>. 50 Sprague\u2010Dawley rats were randomly divided into the following groups: the sham operation group (sham group), HF model group (HF group), HF+<jats:italic>\u03ba<\/jats:italic>\u2010OR agonist U50488 group (HU group), HF+U50488H+novel calmodulin\u2010dependent protein kinase II (CaMKII) agonist (oleic acid) (HUO group), and HF+U50488H+Nrf2 inhibitor (HUM group). The HF rat\u2019s model was established through surgical ligation of the left anterior descending coronary artery and the exhausting swimming exercise. After that, rat\u2019s cardiac function was monitored by echocardiography. HE and MASSON staining was used to detect the myocardial injury, and TUNEL staining was used to detect the myocardial apoptosis. ELISA was performed to detect the biomarkers of oxidative stress. Moreover, the distribution of reactive oxygen species (ROS) and Nrf2 was detected under immunofluorescence. The expression of sarco\/endoplasmic reticulum calcium (Ca<jats:sup>2+<\/jats:sup>) ATPase (SERCA) 2a, calmodulin, endoplasmic reticulum stress\u2010 (ERS\u2010) related proteins, and Nrf2\/HO\u20101 signaling pathway\u2010related proteins were detected by Western Blotting. <jats:italic>Results<\/jats:italic>. <jats:italic>\u03ba<\/jats:italic>\u2010OR agonist U50488H can significantly enhance rat\u2019s cardiac function, reduce the injury and apoptosis of myocardial cells, and alleviate endoplasmic reticulum stress injury in HF rats via upregulating the SERCA2a expression and inhibiting the Ca<jats:sup>2+<\/jats:sup> influx. Furthermore, U50488H could also inhibit the phosphorylation of CaMKII and cAMP\u2010response element binding protein (CREB). Additionally, administration of CaMKII\u2010specific agonist could partially block the therapeutic effect of <jats:italic>\u03ba<\/jats:italic>\u2010OR agonist on the myocardium of HF rats. Interestingly, the antagonist of Nrf2 could also significantly reverse the therapeutic effect of <jats:italic>\u03ba<\/jats:italic>\u2010OR agonist. Therefore, these results suggested that the effect of U50488H on HF rats is dependent on regulating CaMKII phosphorylation and activating the Nrf2\/HO\u20101 pathway. <jats:italic>Conclusion<\/jats:italic>. <jats:italic>\u03ba<\/jats:italic>\u2010OR agonists U50488H can improve ERS in cardiomyocytes and relieve myocardial injury in HF rats through activating the Nrf2\/HO\u20101 pathway and regulating Ca<jats:sup>2+<\/jats:sup>\u2010SERCA2a to inhibit Ca<jats:sup>2+<\/jats:sup> influx.<\/jats:p>","DOI":"10.1155\/2021\/7328437","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T04:35:09Z","timestamp":1627792509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<i>\u03ba<\/i> Opioid Receptor Agonist Inhibits Myocardial Injury in Heart Failure Rats through Activating Nrf2\/HO\u20101 Pathway and Regulating 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