毛蕊异黄酮通过调节 miR-146a-5p/NRP2/SSH1 轴减轻脂多糖诱导的脓毒症血管内皮功能障碍。
Ruscogenin Attenuates Lipopolysaccharide-Induced Septic Vascular Endothelial Dysfunction by Modulating the miR-146a-5p/NRP2/SSH1 Axis.
机构信息
Emergency Care Unit, The First People's Hospital of Wenling, Wenling, Zhejiang, 317500, People's Republic of China.
Emergency Department, The First People's Hospital of Wenling, Wenling, Zhejiang, 317500, People's Republic of China.
出版信息
Drug Des Devel Ther. 2022 Apr 12;16:1099-1106. doi: 10.2147/DDDT.S356451. eCollection 2022.
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.
简介
内皮功能障碍（ED）与脓毒症的进展有关。毛蕊异黄酮（RUS）在治疗 ED 和脓毒症方面显示出相当大的疗效。在本研究中，评估了 RUS 对脓毒症引起的 ED 的影响，并通过关注 RUS 与 miRNAs 的相互作用来探讨其机制。
方法
使用 LPS 法在小鼠和人脐静脉内皮细胞（HUVEC）中诱导脓毒症。确定对脓毒症有反应的 miRNAs 的表达谱。用 RUS 治疗后，检查与脓毒症和 ED 相关的症状。分析小鼠存活率、动脉结构、全身炎症、细胞活力、凋亡以及 miR-146a-5p/NRP2/SSH1 轴的变化。
结果
基于微阵列结果，选择 miR-146a-5p 作为治疗靶点。RUS 提高了脓毒症小鼠的存活率和动脉结构，抑制了促炎细胞因子，下调了 miR-146a-5p，上调了 NPR2 和 SSH1。在 HUVEC 中，RUS 增加了细胞活力，抑制了细胞凋亡，抑制了炎症，下调了 miR-146a-5p，增加了 NRP2 和 SSH1 水平。重新诱导 miR-146a-5p-5p 会损害 RUS 对 HUVEC 的保护作用。
讨论
RUS 对脓毒症引起的内皮损伤的作用依赖于对 miR-146a-5p 的抑制。
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