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脂多糖诱导急性呼吸窘迫综合征的新型树鼩模型。

A novel tree shrew model of lipopolysaccharide-induced acute respiratory distress syndrome.

机构信息

Institute of Laboratory Animal Science, Jinan University, Guangzhou, China.

Institute of Laboratory Animal Science, Jinan University, Guangzhou, China.

出版信息

J Adv Res. 2024 Feb;56:157-165. doi: 10.1016/j.jare.2023.03.009. Epub 2023 Apr 8.

DOI:10.1016/j.jare.2023.03.009
PMID:37037373
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10834818/
Abstract

INTRODUCTION

Acute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure, with substantial attributable morbidity and mortality. The small animal models that are currently used for ARDS do not fully manifest all of the pathological hallmarks of human patients, which hampers both the studies of disease mechanism and drug development.

OBJECTIVES

To examine whether the phenotypic changes of primate-like tree shrews in response to a one-hit lipopolysaccharides (LPS) injury resemble human ARDS features.

METHODS

LPS was administered to tree shrews through intratracheal instillation; then, the animals underwent CT or PET/CT imaging to examine the changes in the structure and function of the whole lung. The lung histology was analyzed by H&E staining and immunohistochemical staining of inflammatory cells.

RESULTS

Results demonstrated that tree shrews exhibited an average survival time of 3-5 days after LPS insult, as well as an obvious symptom of dyspnea before death. The ratios of PaO to FiO (P/F ratio) were close to those of moderate ARDS in humans. CT imaging showed that the scope of the lung injury in tree shrews after LPS treatment were extensive. PET/CT imaging with F-FDG displayed an obvious inflammatory infiltration. Histological analysis detected the formation of a hyaline membrane, which is usually present in human ARDS.

CONCLUSION

This study established a lung injury model with a primate-like small animal model and confirmed that they have similar features to human ARDS, which might provide a valuable tool for translational research.

摘要

简介

急性呼吸窘迫综合征(ARDS)是呼吸衰竭的主要原因,具有较高的发病率和死亡率。目前用于 ARDS 的小动物模型并不能完全表现出人类患者的所有病理特征,这阻碍了疾病机制的研究和药物的开发。

目的

检查灵长类树鼩对单次脂多糖(LPS)损伤的表型变化是否类似于人类 ARDS 的特征。

方法

通过气管内滴注将 LPS 给予树鼩;然后,对动物进行 CT 或 PET/CT 成像,以检查整个肺的结构和功能变化。通过 H&E 染色和炎症细胞的免疫组织化学染色分析肺组织学。

结果

结果表明,LPS 攻击后树鼩的平均存活时间为 3-5 天,并且在死亡前出现明显的呼吸困难症状。氧分压与吸入氧浓度比值(P/F 比值)接近人类中度 ARDS 的比值。CT 成像显示 LPS 处理后的树鼩肺损伤范围广泛。用 F-FDG 进行的 PET/CT 成像显示出明显的炎症浸润。组织学分析检测到透明膜的形成,这在人类 ARDS 中通常存在。

结论

本研究建立了一种具有灵长类小动物模型的肺损伤模型,并证实它们与人 ARDS 具有相似的特征,这可能为转化研究提供有价值的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/9670b54bd161/fx3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/65159aa7a6d6/fx2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/9670b54bd161/fx3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/e4e68455577a/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/63faef26041d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/4376dd6cf465/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/5710de9aac3e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/13cd354fcc3c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/de2ee543ccc7/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/f133b28ce68a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/7d5638653818/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/65159aa7a6d6/fx2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bb/10834818/9670b54bd161/fx3.jpg

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