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胶原结合型 FGF2 对弹性蛋白酶诱导的肺损伤的早期和晚期干预效果。

The early and late intervention effects of collagen-binding FGF2 on elastase-induced lung injury.

机构信息

Beijing University of Chinese Medicine, Beijing 100029, China; Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Peking Union Medical College, Beijing 100029, China.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Biomed Pharmacother. 2023 Feb;158:114147. doi: 10.1016/j.biopha.2022.114147. Epub 2022 Dec 28.

Abstract

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) has high morbidity and mortality, with no effective treatment at present. Emphysema, a major component of COPD, is a leading cause of human death worldwide. Fibroblast growth factor 2 (FGF2) is implicated in the pathogenesis of pulmonary emphysema and may play an important role in the lung repair process after injury, but concerns remain with respect to its effectiveness.

OBJECTIVE

In the present work, we sought to determine how the timing (early and late intervention) of sustained-release FGF2 system administration impacted its effectiveness on a porcine pancreatic elastase (PPE)-induced lung injury mouse model.

METHODS

To examine the early intervention efficiency of collagen-binding FGF2 (CBD-FGF2), mice received intratracheally nebulized CBD-FGF2 with concurrent intratracheal injection of PPE. To explore the late intervention effect, CBD-FGF2 was intratracheally aerosolized after PPE administration, and lungs were collected after CBD-FGF2 treatment for subsequent analysis.

RESULT

In response to PPE, mice had significantly increased alveolar diameter, collagen deposition and expression of inflammatory factors and decreased lung function indices and expression of alveolar epithelium markers. Our results indicate that CBD-FGF2 administration was able to prevent and repair elastase-induced lung injury partly through the suppression of the inflammatory response and recovery of the alveolar epithelium. The early use of CBD-FGF2 for the prevention of PPE-induced emphysema showed better results than late therapeutic administration against established emphysema.

CONCLUSION

These data provide insight regarding the prospective role of a drug-based option (CBD-FGF2) for preventing and curing emphysema.

摘要

简介

慢性阻塞性肺疾病(COPD)发病率和死亡率高,目前尚无有效治疗方法。肺气肿是 COPD 的主要组成部分,是全球人类死亡的主要原因。成纤维细胞生长因子 2(FGF2)与肺气肿的发病机制有关,在损伤后的肺修复过程中可能发挥重要作用,但仍存在有效性问题。

目的

本研究旨在探讨持续释放 FGF2 系统给药的时机(早期和晚期干预)对猪胰弹性蛋白酶(PPE)诱导的肺损伤小鼠模型的有效性的影响。

方法

为了检验胶原结合 FGF2(CBD-FGF2)的早期干预效果,我们在气管内滴注 PPE 的同时,经气管内滴注 CBD-FGF2。为了探索晚期干预效果,在给予 PPE 后,经气管内雾化 CBD-FGF2,然后在给予 CBD-FGF2 治疗后收集肺部进行后续分析。

结果

在 PPE 作用下,小鼠的肺泡直径、胶原沉积和炎症因子表达显著增加,肺功能指数和肺泡上皮标志物表达降低。我们的结果表明,CBD-FGF2 给药部分通过抑制炎症反应和恢复肺泡上皮来预防和修复弹性蛋白酶诱导的肺损伤。早期使用 CBD-FGF2 预防 PPE 诱导的肺气肿的效果优于晚期治疗已建立的肺气肿。

结论

这些数据为基于药物的选择(CBD-FGF2)预防和治疗肺气肿的预期作用提供了见解。

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