Department of Icu (Intensive Care Unit), The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
The First Clinical Medical College of Jinan University, Guangzhou, China.
Bioengineered. 2022 Mar;13(3):7168-7180. doi: 10.1080/21655979.2022.2034583.
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.
研究揭示了组蛋白去乙酰化酶（HDACs）/microRNAs（miRNAs）与脓毒症之间的关系，但很少有研究探讨 HDAC1/miR-124-5p 在脓毒症中的作用机制。本研究通过调控高迁移率族蛋白 B1（HMGB1）探讨 HDAC1/miR-124-5p 对脓毒症小鼠心肌损伤的影响。通过盲肠结扎穿孔法诱导脓毒症小鼠模型，检测脓毒症小鼠心肌组织中 HDAC1、miR-124-5p 和 HMGB1 的表达。注射 HDAC1 低表达、miR-124-5p 高表达或 HMGB1 低表达相关结构物，观察脓毒症小鼠心功能、炎症反应、氧化应激反应、心肌组织病理变化及细胞凋亡情况。验证 HDAC1/miR-124-5p/HMGB1 之间的关系。结果显示，脓毒症小鼠心肌组织中 HDAC1 和 HMGB1 表达上调，miR-124-5p 表达下调。恢复 miR-124-5p/敲低 HDAC1 或 HMGB1 可恢复脓毒症小鼠的心功能，改善心脏功能，减轻炎症反应，缓解氧化应激反应，减轻心肌组织病理损伤，抑制心肌细胞凋亡。HDAC1 与 miR-124-5p 结合，miR-124-5p 直接靶向 HMGB1。综上，下调 HDAC1 或上调 miR-124-5p 通过降低 HMGB1 恢复脓毒症小鼠的心肌损伤。
