Biomedicine & Pharmacotherapy (Apr 2019)
Protective effect of down-regulated microRNA-27a mediating high thoracic epidural block on myocardial ischemia-reperfusion injury in mice through regulating ABCA1 and NF-κB signaling pathway
Abstract
Introduction: Myocardial ischemia-reperfusion injury (MI/RI) is linked with serious inflammatory response, which may lead to myocyte injury. The important role of miR-27a in MI/RI has been previously demonstrated. Therefore, this study aims to investigate the effect of miR-27a targeting ABCA1 on MI/RI by investigating its influences on high thoracic epidural block (HTEB) mediated by the NF-κB signaling pathway. Methods: A MI/RI mouse model and a MI/RI with HTEB mouse model were established to observed the histopathological changes and ultrastructure of myocardial tissues and assess the positive expression of ABCA1. Cardiac troponin T (cTnT), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined using enzyme-linked immunosorbent assay (ELISA). The expression of miR-27a, ABCA1, IκBα and p65 in myocardial cells that transfected with different mimic, inhibitor and siRNAs was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot, with cell apoptosis analyzed by flow cytometry. Results: ABCA1 was a target gene of miR-27a and was lowly expressed in myocardial tissues of MI/RI mice. The decreased content of cTnT, TNF-α and IL-1β and expression of miR-27a and p65 as well as increased expression of ABCA1 and IκBα were revealed in myocardial tissues of MI/RI mice with HTEB. miR-27a negatively regulated the expression of ABCA1, and inhibition of miR-27a could activated NF-κB pathway by up-regulating ABCA1 which contribute to suppressed myocardial cell apoptosis according to demonstration of elevated ABCA1 and IκBα, and decreased p65 in myocardial cell that transfected with miR-27a inhibitor. Conclusion: Collectively, our study indicates that inhibition of miR-27a could induce HTEB to protect mice against MI/RI by regulating ABCA1 and NF-κB signaling pathway.
