OEA alleviates apoptosis in diabetic rats with myocardial ischemia/reperfusion injury by regulating the PI3K/Akt signaling pathway through activation of TRPV1

Enhui Yao; Lili Luo; Chenxi Lin; Jing Wen; Yanglongfei Li; Tong Ren; Yujie Chen; Jinhua Huang; Xin Jin

doi:10.3389/fphar.2022.964475

OEA alleviates apoptosis in diabetic rats with myocardial ischemia/reperfusion injury by regulating the PI3K/Akt signaling pathway through activation of TRPV1

Front Pharmacol. 2022 Nov 14:13:964475. doi: 10.3389/fphar.2022.964475. eCollection 2022.

Authors

Enhui Yao¹, Lili Luo², Chenxi Lin³, Jing Wen², Yanglongfei Li¹, Tong Ren², Yujie Chen¹, Jinhua Huang¹, Xin Jin²

Affiliations

¹ Department of Cardiology, Fujian Medical University Union Hospital, Fujian Institute of Coronary Artery Disease, Fujian Heart Medical Center, Fuzhou, China.
² Xiamen Key Laboratory of Chiral Drugs, School of Medicine, Xiamen University, Xiamen, China.
³ Department of Pediatrics, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Abstract

Reperfusion therapy after myocardial infarction may lead to myocardial injury, which can be complicated and exacerbated by diabetes. The existing therapeutic methods for myocardial ischemia-reperfusion injury (MIRI) in diabetic patients are not ideal. Oleoylethanolamide (OEA) has been found to have protective effects on diabetes and acute cerebral ischemia. This study aimed to determine whether OEA can alleviate MIRI in diabetic rats, and to explore the underlying mechanism. The model of diabetic rats with MIRI was established by blocking the left coronary artery for 30 min, followed by restoring blood flow stability for 120 min. The myocardial enzyme spectrum, area of MIRI, and expression levels of apoptosis-related proteins were detected. The results showed that OEA pretreatment could reduce myocardial infarction area, protect myocardial tissue structure, and reduce myocardial cell apoptosis in diabetic rats with MIRI. Meanwhile, the levels of creatine kinase (CK)-MB (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were reduced, while superoxide dismutase (SOD) level was elevated. H9C2 cells were treated with high glucose and oxygen-glucose deprivation/reperfusion (OGD/R) to establish an in vitro model. Capsazepine (CPZ), an antagonist of transient receptor potential vanilloid subtype 1 (TRPV1), and LY294002, an inhibitor of PI3K, were used to treat H9C2 cells in vitro. Apoptosis level and the expression levels of apoptosis-related proteins were measured. It was found that OEA activated TRPV1 and the PI3K/Akt signaling pathway, downregulated the expression levels of apoptosis-related proteins (Bcl-2 and cleaved caspase-3), and ameliorated the apoptosis of H9C2 cells treated with high glucose and OGD/R. This study clarified that OEA, as a TRPV1 agonist, could reduce myocardial cell apoptosis by activating the PI3K/Akt signaling pathway in diabetic rats with MIRI. The findings may provide a theoretical basis for administration of OEA as a potential therapeutic agent into diabetic patients with MIRI.

Keywords: TRPV1; apoptosis; diabetic rats; myocardial ischemia-reperfusion injury; oleoylethanolamide.