Alveolar macrophages polarization switch via α₂-adrenoceptor activation ameliorates pulmonary inflammation following kidney ischemia reperfusion.

IF 4.8 3区医学 Q2 CELL BIOLOGY

Inflammation Research Pub Date : 2025-04-17 DOI:10.1007/s00011-025-02029-0

Jieyu Li, Zhigang Qin, Xinhai He, Ling Jiang, Xiangfeng Liu, Zhengwei Xue, Xiao Li, Yueming Xu, Peng Li, Jianteng Gu

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引用次数: 0

Abstract

Purpose: The present study aimed to explore the anti-inflammatory mechanism of dexmedetomidine (Dex), an α₂-adrenoceptor (α₂-AR) agonist, in renal ischemia-reperfusion (RIR)-induced acute lung injury (ALI).

Methods: RIR was induced in C57BL/6J mice by bilateral renal pedicles occlusion for 60 min followed by 24 h of reperfusion. Mice were pretreated with Dex alone or in combination with atipamezole (Atip), an α₂-AR antagonist. Pulmonary histopathological assessment, arterial blood gas analysis, cell count and multiple cytokine examination in bronchoalveolar lavage fluid (BALF), evaluation of the global inflammation status in lung tissue, and investigation of alveolar macrophage phenotypes were carried out. In vitro, the polarization of mouse alveolar macrophages (MH-S) treated with serum from normal or RIR mice was indirectly detected by quantitative polymerase chain reaction (qPCR).

Results: The findings demonstrated that, in comparison to RIR animals, dexmedetomidine mitigated lung injury and remarkably promoted macrophage polarization towards an anti-inflammatory M2 phenotype in the pulmonary tissue. Concurrently, a reduction in inflammatory cell infiltration and levels of pro-inflammatory cytokines was observed. In vitro studies verified that dexmedetomidine directed MH-S towards the M2 phenotype after stimulation with RIR serum. However, these effects were mostly reversed following administration of atipamezole.

Conclusion: Dexmedetomidine alleviates renal ischemia-reperfusion-induced ALI by activating α₂-adrenoceptor, thereby inducing macrophage polarization towards an anti-inflammatory phenotype and reducing pulmonary global inflammation.

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α - 2肾上腺素能受体激活肺泡巨噬细胞极化开关改善肾缺血再灌注后肺部炎症。

目的：探讨α2-肾上腺素能受体（α2-AR）激动剂右美托咪定（Dex）在肾缺血再灌注（RIR）诱导的急性肺损伤（ALI）中的抗炎作用机制。方法：C57BL/6J小鼠双侧肾蒂阻断60 min，再灌注24 h诱导RIR。小鼠分别单独或联合α2-AR拮抗剂阿替帕唑（atipamezole, Atip）进行预处理。进行肺组织病理学评估、动脉血气分析、支气管肺泡灌洗液（BALF）细胞计数及多种细胞因子检测、肺组织整体炎症状态评估、肺泡巨噬细胞表型研究。在体外，采用定量聚合酶链反应（qPCR）间接检测正常或RIR小鼠血清处理小鼠肺泡巨噬细胞（h - s）的极化情况。结果：研究结果表明，与RIR动物相比，右美托咪定减轻了肺损伤，并显著促进肺组织中巨噬细胞向抗炎M2表型极化。同时，观察到炎症细胞浸润和促炎细胞因子水平的减少。体外研究证实右美托咪定在RIR血清刺激后使MH-S向M2表型转变。然而，在服用阿替帕唑后，这些效果大多被逆转。结论：右美托咪定通过激活α2-肾上腺素能受体，诱导巨噬细胞向抗炎表型极化，减轻肺全局性炎症，减轻肾缺血再灌注诱导的ALI。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammation Research 医学-免疫学

CiteScore

9.90

自引率

1.50%

发文量

134

审稿时长

3-8 weeks

期刊介绍： Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.