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肺泡液对水通道蛋白和 Na+/K+-ATP 酶的影响及其可能的理论或临床意义。

Influence of Alveolar Fluid on Aquaporins and Na+/K+-ATPase and Its Possible Theoretical or Clinical Significance.

机构信息

Neonatal Intensive Care Unit, Southern Medical University, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China.

Department of Neonatology and NICU, Beijing Chaoyang District Maternal and Child Healthcare Hospital, Beijing, China.

出版信息

Am J Perinatol. 2022 Oct;29(14):1586-1595. doi: 10.1055/s-0041-1724001. Epub 2021 Feb 21.

DOI:10.1055/s-0041-1724001
PMID:33611784
Abstract

OBJECTIVE

Pulmonary edema is the most common pathophysiological change in pulmonary disease. Aquaporins (AQPs) and Na/K-ATPase play pivotal roles in alveolar fluid clearance. This study aimed to explore the influence of increased alveolar fluid on the absorption of lung fluid.

STUDY DESIGN

Eighty New Zealand rabbits were randomly divided into eight groups ( = 10 in each group), and models of different alveolar fluid contents were established by the infusion of different volumes of normal saline (NS) via the endotracheal tube. Five animals in each group were sacrificed immediately after infusion to determine the wet/dry ratio, while the remaining animals in each group were killed 4 hours later to determine the wet/dry ratio at 4 hours. Additionally, lung specimens were collected from each group, and quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemical (IHC) analyses of AQPs and Na/K-ATPase were performed.

RESULTS

The qRT-PCR analysis and western blot studies showed markedly decreased mRNA and protein levels of AQP1 and Na/K-ATPase when the alveolar fluid volume was ≥6 mL/kg, and the mRNA level of AQP5 was significantly reduced when the alveolar fluid volume was ≥4 mL/kg. In addition, IHC analysis showed the same results. At 4 hours, the lung wet/dry ratio was significantly increased when the alveolar fluid volume was ≥6 mL/kg; however, compared with 0 hours after NS infusion, there was still a significant absorption of alveolar fluid for a period of 4 hours.

CONCLUSION

The results of this study suggest that increased alveolar fluid may induce the downregulation of the mRNA and protein expression of AQPs and Na/K-ATPase, which appear to affect alveolar fluid clearance in rabbit lungs. Early intervention is required to avoid excessive alveolar fluid accumulation.

KEY POINTS

· The expression levels of AQPs and Na+/K+--ATPase were significantly decreased as alveolar fluid increased.. · At 4 hours, wet/dry ratio was significantly increased when infusion volume was ≥ 6 mL/kg.. · Early intervention is required to avoid excessive alveolar fluid accumulation..

摘要

目的

肺水肿是肺部疾病中最常见的病理生理改变。水通道蛋白(AQP)和 Na/K-ATP 酶在肺泡液体清除中起关键作用。本研究旨在探讨增加的肺泡液对肺液吸收的影响。

研究设计

80 只新西兰兔随机分为 8 组(每组 10 只),通过气管内管输注不同体积的生理盐水(NS)建立不同肺泡液含量的模型。每组中的 5 只动物在输注后立即处死以确定湿/干比,而每组中的其余动物在 4 小时后处死以确定 4 小时时的湿/干比。此外,从每组收集肺标本,并进行 AQP 和 Na/K-ATP 酶的定量实时 PCR(qRT-PCR)、western blot 和免疫组化(IHC)分析。

结果

qRT-PCR 分析和 western blot 研究表明,当肺泡液量≥6mL/kg 时,AQP1 和 Na/K-ATP 酶的 mRNA 和蛋白水平明显降低,当肺泡液量≥4mL/kg 时,AQP5 的 mRNA 水平显著降低。此外,IHC 分析也得到了相同的结果。4 小时时,当肺泡液量≥6mL/kg 时,肺湿/干比明显增加;然而,与 NS 输注后 0 小时相比,在 4 小时内仍有明显的肺泡液吸收。

结论

本研究结果表明,增加的肺泡液可能导致 AQP 和 Na/K-ATP 酶的 mRNA 和蛋白表达下调,这似乎影响兔肺的肺泡液体清除。需要早期干预以避免肺泡液过度积聚。

关键点

·肺泡液增加时 AQP 和 Na+/K+--ATP 酶的表达水平明显降低。·输注量≥6mL/kg 时,4 小时时湿/干比明显增加。·需要早期干预以避免肺泡液过度积聚。

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