LncRNA DLEU1 contributes to the progression of septic myocardial dysfunction by targeting miR-381-3p.

Abstract

Introduction: Cardiac dysfunction is a common complication of sepsis. This study aimed to elucidate the regulatory effect of DLEU1 on sepsis-induced myocardial injury.

Material and methods: HL-1 cardiomyocytes were treated with lipopolysaccharide (LPS) to mimic sepsis-induced myocardial injury in vitro, and the mouse septic model was established through cecum ligation and perforation (CLP). Cell viability was evaluated using Cell Counting Kit-8 (CCK-8), while apoptosis was assessed via Annexin-V staining. Pro-inflammatory factors including tumor necrosis factor α (TNF-α), interleukin (IL)-1 β, IL-6, and oxidative stress indicators were detected by ELISA kits. Cardiac function in mice was determined using cardiac ultrasound, and myocardial indices were detected by ELISA.

Results: DLEU1 levels were up-regulated gradually in HL-1 cardiomyocytes after LPS treatment in a dose-dependent manner, along with the overactivation of inflammatory responses and oxidative stress. DLEU1 downregulation alleviated LPS-induced cell apoptosis, inflammatory response and oxidative stress. In vivo, DLEU1 knockdown improved the cardiac function of septic mice, and alleviated inflammation and oxidative stress. MiR-381-3p, acting as a competing endogenous RNA (ceRNA) of DLEU1, reversed the effects of DLEU1 in both septic cell and mouse models.

Conclusions: The results indicate that the DLEU1/miR-381-3p axis is an intrinsic regulator of myocardial injury in sepsis.