Eclipta prostrata improves alveolar development of bronchopulmonary dysplasia via suppressing the NLRP3 inflammasome in a DLD-dependent manner.

IF 2.7 3区医学 Q1 PEDIATRICS

Pediatric Pulmonology Pub Date : 2024-12-01 Epub Date: 2024-08-08 DOI:10.1002/ppul.27209

Xiaoyan Zheng, Zhen Tan, Danying Zhu, Dongying Zhao, Chengbo Liu, Shunchun Wang, Xingyun Wang, Yongjun Zhang

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引用次数: 0

Abstract

Objectives: Bronchopulmonary dysplasia (BPD), the most common late morbidity in preterm infants, is characterized by impaired alveolar development caused by persistent lung inflammation. Studies have shown that NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome-mediated inflammation is critically involved in the development of BPD. As a traditional Chinese medicinal herb, Eclipta prostrata (EAP) exhibits potent anti-inflammatory properties. Our study aims to investigate whether EAP could improve the lung development of BPD by suppressing the lung inflammatory response.

Methods: The BPD rat model was established by intra-amniotic injection of lipopolysaccharide (LPS) and postnatal exposure to hyperoxia. Changes in the NLRP3 inflammasome and pyroptosis were assessed by treatment with EAP. The effect of EAP on the NLRP3 inflammasome was tested in vitro using the THP-1 cell line and primary alveolar macrophages. Proteomics analysis was used to elucidate the mechanism of action of EAP.

Results: Histopathological and immunofluorescence results of lung tissues revealed that LPS and hyperoxia induced lung injury and triggered NLRP3 inflammasome activation and pyroptosis in alveolar macrophages. EAP ameliorated BPD lung injury, inhibited NLRP3 inflammasome activation and reduced gasdermin D (GSDMD) expression in alveolar macrophages. EAP downregulated the expression of NLRP3 inflammasome pathway molecules (NLRP3, caspase-1, and IL-1β) and GSDMD in LPS-stimulated THP-1 macrophages and primary alveolar macrophages. In addition, proteomics analysis identified that dihydrolipoamide dehydrogenase (DLD) interacted with EAP. Inhibition of DLD activity abolished the protective effects of EAP.

Conclusions: Our study suggested that EAP could attenuate arrest of alveolar development via inhibiting NLRP3 inflammasome in a DLD-dependent way, and could be a potential therapeutic method for BPD.

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Eclipta prostrata通过抑制NLRP3炎性体，以DLD依赖性方式改善支气管肺发育不良的肺泡发育。

目的：支气管肺发育不良（BPD）是早产儿最常见的晚期疾病，其特点是肺部炎症持续存在导致肺泡发育受损。研究表明，NOD-、LRR-和含吡咯啉结构域 3（NLRP3）炎症体介导的炎症与 BPD 的发展密切相关。作为一种传统中草药，Eclipta prostrata（EAP）具有强大的抗炎特性。我们的研究旨在探讨 EAP 是否能通过抑制肺部炎症反应来改善 BPD 的肺部发育：方法：通过羊膜内注射脂多糖（LPS）和出生后暴露于高氧环境建立 BPD 大鼠模型。方法：通过羊膜内注射脂多糖（LPS）和出生后暴露于高氧环境，建立了BPD大鼠模型。在体外使用THP-1细胞系和原发性肺泡巨噬细胞测试了EAP对NLRP3炎性体的影响。蛋白质组学分析用于阐明 EAP 的作用机制：结果：肺组织的组织病理学和免疫荧光结果显示，LPS和高氧诱导肺损伤，并引发肺泡巨噬细胞的NLRP3炎性体活化和脓毒症。EAP 可改善 BPD 肺损伤，抑制 NLRP3 炎性体的活化，并降低肺泡巨噬细胞中 gasdermin D（GSDMD）的表达。EAP 下调了 LPS 刺激的 THP-1 巨噬细胞和原发性肺泡巨噬细胞中 NLRP3 炎性体通路分子（NLRP3、caspase-1 和 IL-1β）和 GSDMD 的表达。此外，蛋白质组学分析发现二氢脂酰胺脱氢酶（DLD）与 EAP 相互作用。抑制 DLD 的活性可消除 EAP 的保护作用：我们的研究表明，EAP可通过抑制NLRP3炎症小体以DLD依赖的方式减轻肺泡发育的停滞，可作为BPD的一种潜在治疗方法。

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

Pediatric Pulmonology 医学-呼吸系统

CiteScore

6.00

自引率

12.90%

发文量

468

审稿时长

3-8 weeks

期刊介绍： Pediatric Pulmonology (PPUL) is the foremost global journal studying the respiratory system in disease and in health as it develops from intrauterine life though adolescence to adulthood. Combining explicit and informative analysis of clinical as well as basic scientific research, PPUL provides a look at the many facets of respiratory system disorders in infants and children, ranging from pathological anatomy, developmental issues, and pathophysiology to infectious disease, asthma, cystic fibrosis, and airborne toxins. Focused attention is given to the reporting of diagnostic and therapeutic methods for neonates, preschool children, and adolescents, the enduring effects of childhood respiratory diseases, and newly described infectious diseases. PPUL concentrates on subject matters of crucial interest to specialists preparing for the Pediatric Subspecialty Examinations in the United States and other countries. With its attentive coverage and extensive clinical data, this journal is a principle source for pediatricians in practice and in training and a must have for all pediatric pulmonologists.