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BMC Cardiovasc Disord ; 23(1): 154, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36964482

RESUMO

PURPOSE: This study aimed to determine the effect and mechanism of action of adenosine 2 receptor (A2R) activation on myocardial ischemia reperfusion injury (MIRI) under diabetic conditions. METHODS: MIRI type 2 diabetic rats and H9C2 cardiomyocytes were treated with A2R agonist and then subjected to hypoxia for 6 h and reoxygenation for 18 h. Myocardial damage, and infarct size were determined by cardiac ultrasound. Indicators of cardiomyocyte injury, creatine kinase-MB and cardiac troponin I were detected by Enzyme Linked Immunosorbent Assay. Endoplasmic reticulum stress (ERS) was determined through measuring the expression levels of ERS related genes GRP78, p-IRE1/IRE1, and p-JNKJNK. The mechanism of A2R cardio protection in MIRI through regulating ERS induced autophagy was determined by investigating the ER resident protein IRE-1. The ER-stress inducer Tunicamycin, and the IRE-1 inhibitor STF in combination with the A2R agonist NECA were used, and the cellular responses were assessed through autophagy proteins expression Beclin-1, p62, LC3 and apoptosis. RESULTS: NECA improved left ventricular function post MIRI, limited myocardial infarct size, reduced myocardial damage, decreased cardiomyocytes apoptosis, and attenuated ERS induced autophagy through regulating the IRE-XBP1s-CHOP pathway. These actions resulted into overall protection of the myocardium against MIRI. CONCLUSION: In summary, A2R activation by NECA prior to ischemia attenuates apoptosis, reduces ERS induced autophagy and restores left ventricular function. This protective effect occurs through regulating the IRE1-XBPs-CHOP related mechanisms. NECA is thus a potential target for the treatment of MIRI in patient with type 2 diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Traumatismo por Reperfusão Miocárdica , Ratos , Animais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Adenosina-5'-(N-etilcarboxamida)/metabolismo , Adenosina-5'-(N-etilcarboxamida)/farmacologia , Ratos Sprague-Dawley , Miócitos Cardíacos/metabolismo , Apoptose , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/farmacologia , Autofagia
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