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菊苣酸通过 Nrf2/HO-1 信号通路抑制铁死亡对 LPS 诱导的小鼠子宫内膜炎的保护作用。

Protective effects of chicoric acid on LPS-induced endometritis in mice via inhibiting ferroptosis by Nrf2/HO-1 signal axis.

机构信息

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

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

出版信息

Int Immunopharmacol. 2022 Dec;113(Pt B):109435. doi: 10.1016/j.intimp.2022.109435. Epub 2022 Nov 17.

Abstract

Chicoric acid (CA), a natural phenolic acid extracted from Mediterranean vegetable chicory, has anti-oxidative effect. We aimed to investigate the effects of CA on endometritis and clarify the underlying mechanism. C57BL/6 mice were divided into five groups: control group, LPS group, and LPS + CA groups. All mice except control group were infused of LPS into the uterus. The mice of LPS + CA groups were intraperitoneally injected CA 1 h before LPS challenge. CA significantly alleviatedLPS-induced pathological damage, MPO activity, and inflammatory cytokine production. CA significantly suppressed ferroptosis in LPS-induced endometritis. CA also attenuated LPS-induced NF-κB activation. Furthermore, Nrf2 and HO-1 expression were increased by CA. Moreover, the inhibition of CA on LPS-induced endometritis and ferroptosis were markedly prevented in Nrf2 knockdown mice. In conclusion, the results suggested CA protected mice against LPS-induced endometritisthrough inhibiting ferroptosis via Nrf2/HO-1 signaling pathway.

摘要

菊苣酸(CA)是一种从地中海蔬菜菊苣中提取的天然酚酸,具有抗氧化作用。本研究旨在探讨 CA 对子宫内膜炎的作用,并阐明其潜在机制。C57BL/6 小鼠分为 5 组:对照组、LPS 组、LPS+CA 组。除对照组外,所有小鼠均向子宫内注入 LPS。LPS+CA 组小鼠在 LPS 攻击前 1 小时腹腔内注射 CA。CA 显著减轻 LPS 诱导的病理损伤、MPO 活性和炎症细胞因子的产生。CA 显著抑制 LPS 诱导的子宫内膜炎中铁死亡。CA 还减弱 LPS 诱导的 NF-κB 激活。此外,CA 增加了 Nrf2 和 HO-1 的表达。此外,Nrf2 敲低小鼠中 CA 对 LPS 诱导的子宫内膜炎和铁死亡的抑制作用明显减弱。总之,研究结果表明 CA 通过 Nrf2/HO-1 信号通路抑制铁死亡来保护 LPS 诱导的子宫内膜炎。

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