Ruscogenin Attenuates Lipopolysaccharide-Induced Septic Vascular Endothelial Dysfunction by Modulating the miR-146a-5p/NRP2/SSH1 Axis.

INTRODUCTION

Endothelial dysfunction (ED) is associated with the progression of sepsis. Ruscogenin (RUS) has shown considerable efficacy in treating ED and sepsis. In the current study, the effects of RUS on sepsis-induced ED were assessed, and the mechanism was explored by focusing on the interactions of RUS with miRs.

METHODS

Sepsis was induced in mice and in human umbilical vein endothelial cells (HUVECs) using LPS method. Expression profile of miRs responding to sepsis was determined. Symptoms associated with sepsis and ED were examined after treatment with RUS. Changes in mouse survival, arterial structure, systemic inflammation, cell viability, apoptosis, and the miR-146a-5p/NRP2/SSH1 axis were analyzed.

RESULTS

Based on the microarray results, miR-146a-5p was selected as the therapeutic target. RUS improved survival rates and arterial structure, suppressed proinflammatory cytokines, down-regulated miR-146a-5p, and up-regulated NPR2 and SSH1 in septic mice. In HUVECs, RUS increased cell viability, suppressed apoptosis, inhibited inflammation, downregulated miR-146a-5p, and increased NRP2 and SSH1 levels. The re-induction of miR-146a-5p-5p impaired the protective effects of RUS on HUVECs.

DISCUSSION

Effects of RUS on sepsis-induced impairments in endothelium relied on the suppression of miR-146a-5p.