Down-regulated HDAC1 and up-regulated microRNA-124-5p recover myocardial damage of septic mice

Abstract

ABSTRACT Studies have revealed the relationship between histone deacetylases (HDACs)/microRNAs (miRNAs) and sepsis, but little has ever investigated the mechanism of HDAC1/miR-124-5p in sepsis. Herein, we studied the impacts of HDAC1/miR-124-5p on myocardial damage of septic mice via regulating high-mobility group box chromosomal protein 1 (HMGB1). Septic mice were induced by cecal ligation and puncture. HDAC1, miR-124-5p and HMGB1 expression in myocardial tissues of septic mice were detected. Septic mice were injected with HDAC1 low expression-, miR-124-5p high expression- or HMGB1 low expression-related structures to observe cardiac function, inflammatory response, oxidative stress response, myocardial pathological changes and apoptosis in myocardial tissues of septic mice. The relationship of HDAC1/miR-124-5p/HMGB1 was verified. HDAC1 and HMGB1 expression were upregulated while miR-124-5p expression was decreased in myocardial tissues of septic mice. Restored miR-124-5p/depleted HDAC1 or HMGB1 recovered the cardiac function, improved cardiac function, inflammatory response, oxidative stress response, myocardial pathological changes and inhibit ed cardiomyocyte apoptosis in septic mice. HDAC1 bound to miR-124-5p which directly targeted HMGB1. This study suggests that down-regulated HDAC1 or up-regulated miR-124-5p recovers myocardial damage of septic mice via decreasing HMGB1.