柠檬醛通过激活 Nrf2 信号通路抑制铁死亡来防治 LPS 诱导的子宫内膜炎。

Citral protects against LPS-induced endometritis by inhibiting ferroptosis through activating Nrf2 signaling pathway.

机构信息

Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Erdao District, 126 Sendai Street, Changchun, 130033, Jilin Province, China.

Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China.

出版信息

Inflammopharmacology. 2023 Jun;31(3):1551-1558. doi: 10.1007/s10787-023-01211-2. Epub 2023 Apr 3.

DOI:10.1007/s10787-023-01211-2

PMID:37010717

Abstract

INTRODUCTION

Endometritis is the inflammatory condition of the uterus. Citral, a component of lemongrass oil, is known to exhibit anti-inflammatory activity.

AIM

The effects of citral on LPS-induced endometritis were tested and the mechanisms were investigated.

METHODS

LPS-induced endometritis mice model was established and the effects of citral were detected using this model. Inflammatory cytokines were tested by ELISA. Ferroptosis was assessed by detecting GSH, ATP, MDA, and Fe levels. Signaling pathway was tested by western blot analysis.

RESULTS

Citral prevented LPS-induced endometritis through attenuating uterine pathological changes and inflammatory cytokine release. Meanwhile, citral prevents LPS-induced ferroptosis through attenuating MDA and Fe levels, as well as increasing ATP and GSH levels. Furthermore, citral up-regulated Nrf2 and HO-1 expression and attenuated NF-κB activation. In addition, in Nrf2 knockdown mice, the inhibitory roles of citral on ferroptosis and endometritis were largely reversed.

CONCLUSION

Taken together, citral inhibited LPS-induced endometritis through preventing ferroptosis, which were regulated by Nrf2 signaling pathway.

摘要

简介

子宫内膜炎是子宫的炎症性疾病。柠檬醛是柠檬草油的一种成分，已知具有抗炎活性。

目的

测试柠檬醛对 LPS 诱导的子宫内膜炎的作用，并探讨其机制。

方法

建立 LPS 诱导的子宫内膜炎小鼠模型，并使用该模型检测柠檬醛的作用。通过 ELISA 检测炎症细胞因子。通过检测 GSH、ATP、MDA 和 Fe 水平来评估铁死亡。通过 Western blot 分析检测信号通路。

结果

柠檬醛通过减轻子宫组织病理学变化和炎症细胞因子释放来预防 LPS 诱导的子宫内膜炎。同时，柠檬醛通过降低 MDA 和 Fe 水平以及增加 ATP 和 GSH 水平来预防 LPS 诱导的铁死亡。此外，柠檬醛上调 Nrf2 和 HO-1 的表达并抑制 NF-κB 的激活。此外，在 Nrf2 敲低小鼠中，柠檬醛对铁死亡和子宫内膜炎的抑制作用在很大程度上被逆转。