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解析素 E1 及抑制 BLT2 信号通路减轻单肺通气诱导的肺损伤及炎症反应

Resolvin E1 and Inhibition of BLT2 Signaling Attenuate the Inflammatory Response and Improve One-Lung Ventilation-Induced Lung Injury.

机构信息

Department of Anesthesiology, Quzhou People's Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, Zhejiang, China.

出版信息

Immunol Invest. 2024 Nov;53(8):1293-1307. doi: 10.1080/08820139.2024.2399587. Epub 2024 Sep 4.

Abstract

INTRODUCTION

One-lung ventilation (OLV) is a prevalently used technique to sustain intraoperative pulmonary function. Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator, accelerates the resolution of inflammation in the lungs. However, its therapeutic effects on OLV-induced lung injury remain unclear.

METHODS

We initially developed an OLV rat model and treated it with RvE1. Subsequently, we assessed the wet/dry ratio of the lung tissue, performed hematoxylin and eosin staining, and calculated the ratio of polymorphonuclear cells to white blood cells in the bronchoalveolar lavage fluid. Additionally, we assessed apoptosis, inflammatory factor levels, and lung permeability in the rat lung tissues in the RvE1 treated and untreated groups and explored the molecular mechanisms mediated by RvE1.

RESULTS

Our results indicated that RvE1 alleviated lung injury and inflammation and improved lung tissue apoptosis and permeability in OLV rats. Moreover, RvE1 suppressed the expression of the BLT1/2 signaling pathway and its ligands. The use of BLT2 and BLT1 inhibitors (LY255283 and U-75302, respectively) enhanced RvE1's anti-inflammatory effects and reduced lung injury. Furthermore, synergistic treatment with the BLT2 inhibitor and RvE1 provided grater benefits by more effectively inhibiting the NF-kB, p38 MAPK, and ERK pathways.

DISCUSSION

RvE1 and the inhibition of BLT2 signalling reduce the inflammatory response and mitigate OLV-induced lung injury. These findings suggest a novel therapeutic pathway for managing OLV-related complications.

摘要

简介

单肺通气(OLV)是一种常用的维持术中肺功能的技术。解析素 E1(RvE1)是一种专门的促解决脂质介质,可加速肺部炎症的消退。然而,其在 OLV 诱导的肺损伤中的治疗效果尚不清楚。

方法

我们最初开发了 OLV 大鼠模型并对其进行了 RvE1 治疗。随后,我们评估了肺组织的湿/干比,进行了苏木精和伊红染色,并计算了支气管肺泡灌洗液中多形核细胞与白细胞的比值。此外,我们评估了 RvE1 处理和未处理组大鼠肺组织中的细胞凋亡、炎症因子水平和肺通透性,并探讨了 RvE1 介导的分子机制。

结果

我们的结果表明,RvE1 减轻了 OLV 大鼠的肺损伤和炎症,改善了肺组织细胞凋亡和通透性。此外,RvE1 抑制了 BLT1/2 信号通路及其配体的表达。使用 BLT2 和 BLT1 抑制剂(分别为 LY255283 和 U-75302)增强了 RvE1 的抗炎作用并减轻了肺损伤。此外,BLT2 抑制剂与 RvE1 的协同治疗通过更有效地抑制 NF-kB、p38 MAPK 和 ERK 通路提供了更大的益处。

讨论

RvE1 和 BLT2 信号抑制减少了炎症反应并减轻了 OLV 诱导的肺损伤。这些发现为管理 OLV 相关并发症提供了新的治疗途径。

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