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秦皮素通过调节 AKT/ERK/NF-κB 和 RORγt/IL-17 通路改善脂多糖诱导的小鼠急性肺损伤。

Esculetin Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice Via Modulation of the AKT/ERK/NF-κB and RORγt/IL-17 Pathways.

机构信息

Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

College of Medicine, Chang Gung University, Taoyuan, Taiwan.

出版信息

Inflammation. 2020 Jun;43(3):962-974. doi: 10.1007/s10753-020-01182-4.

DOI:10.1007/s10753-020-01182-4
PMID:32170603
Abstract

Esculetin, a coumarin derivative from various natural plants, has an anti-inflammatory property. In the present study, we examined if esculetin has any salutary effects against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Acute lung injury (ALI) was induced via the intratracheal administration of LPS, and esculetin (20 and 40 mg/kg) was given intraperitoneally 30 min before LPS challenge. After 6 h of LPS administration, lung tissues were collected for analysis. Pretreatment with esculetin significantly attenuated histopathological changes, inflammatory cell infiltration, and production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, in the lung tissue. Furthermore, esculetin inhibited the protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-κB) pathways and downregulated the expression of RORγt and IL-17 in LPS-induced ALI. Our results indicated that esculetin possesses anti-inflammatory and protective effects against LPS-induced ALI via inhibition of the AKT/ERK/NF-κB and RORγt/IL-17 pathways.

摘要

七叶灵是一种从各种天然植物中提取的香豆素衍生物,具有抗炎作用。在本研究中,我们研究了七叶灵是否对 LPS 诱导的急性肺损伤(ALI)有治疗作用。通过气管内给予 LPS 诱导急性肺损伤(ALI),在 LPS 攻击前 30 分钟通过腹腔内给予七叶灵(20 和 40mg/kg)。给予 LPS 6 小时后,收集肺组织进行分析。七叶灵预处理显著减轻了肺组织的组织病理学变化、炎症细胞浸润和促炎细胞因子(如肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和 IL-6)的产生。此外,七叶灵抑制了蛋白激酶 B(AKT)、细胞外信号调节激酶(ERK)和核因子-κB(NF-κB)途径,并下调了 LPS 诱导的 ALI 中 RORγt 和 IL-17 的表达。我们的结果表明,七叶灵通过抑制 AKT/ERK/NF-κB 和 RORγt/IL-17 途径,对 LPS 诱导的 ALI 具有抗炎和保护作用。

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