Butorphanol Alleviates Hypoxia/Reoxygenation‐Induced Myocardial Injury by Activating Wnt/β‐Catenin Signal Pathway

ABSTRACT Ischemic heart disease remains a global health problem with high morbidity and mortality. Butorphanol, as a novel opioid, has been discovered with its cardioprotective properties. The purpose of this study was to explore that butorphanol can alleviate hypoxia/reoxygenation (H/R)‐induced myocardial injury by activating the Wnt/β‐catenin signal pathway. In this study, Cell Counting Kit‐8 (CCK‐8), lactate dehydrogenase (LDH) kit, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and Western blotting experiments were performed to observe butorphanol cardioprotective function and expression of Wnt signaling pathway proteins. For the main result, anti‐apoptotic effect and higher expression of Wnt signaling pathway proteins were observed with the increasing concentrations of butorphanol. Compared with the H/R group, higher cellular viability, lower LDH release, and smaller apoptotic cell population were found in the butorphanol group. In addition, expression levels of apoptosis‐related protein Bax and Cleaved Caspase‐3 decreased, and increased expression of Bcl‐2 were observed. Conversely, the protective effects of butorphanol were attenuated in the XAV939 group. In summary, butorphanol attenuates hypoxia/reoxygenation‐induced myocardial injury by activating the Wnt/β‐catenin signal pathway. Our work provides a theoretical basis for butorphanol's myocardial protective function.