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丹参酮 IIA 通过抑制肺水通道蛋白 (AQP) 1 和 AQP5 的表达来改善海水暴露引起的肺损伤。

Tanshinone IIA ameliorates seawater exposure-induced lung injury by inhibiting aquaporins (AQP) 1 and AQP5 expression in lung.

机构信息

Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, Xi'an 710038, PR China.

出版信息

Respir Physiol Neurobiol. 2011 Apr 30;176(1-2):39-49. doi: 10.1016/j.resp.2011.01.005. Epub 2011 Jan 16.

DOI:10.1016/j.resp.2011.01.005
PMID:21244858
Abstract

Aquaporins (AQPs), a family of transmembrane water channels, mediate physiological response to changes of fluid volume and osmolarity. It is still unknown what role of AQPs plays in seawater drowning-induced acute lung injury (ALI) and whether pharmacologic modulation of AQPs could alleviate the severity of ALI caused by seawater aspiration. In our study, the results from RT-PCR and Western blotting showed that intratracheal installation of seawater up-regulated the mRNA and protein levels of AQP1 and AQP5 in lung tissues. Furthermore, we found that treatment of tanshinone IIA (TIIA, one of the main active components from Chinese herb Danshen) significantly reduced the elevation of AQP1 and AQP5 expression induced by seawater in rats, A549 cells and primary alveolar type II cells. Treatment of TIIA also improved lung histopathologic changes and blood-gas indices, and reduced lung edema and vascular leakage. These findings demonstrated that AQP1 and AQP5 might play an important role in the development of lung edema and lung injury, and that treatment with TIIA could significantly alleviate seawater exposure-induced ALI, which was probably through the inhibition of AQP1 and AQP5 over-expression in lungs.

摘要

水通道蛋白(AQP)是一类跨膜水分子通道,介导细胞对细胞外液容量和渗透压变化的生理反应。目前尚不清楚 AQP 在海水溺水导致的急性肺损伤(ALI)中的作用,以及 AQP 的药物调节是否可以减轻海水吸入引起的 ALI 的严重程度。在我们的研究中,RT-PCR 和 Western blot 的结果表明,气管内注入海水可上调肺组织中 AQP1 和 AQP5 的 mRNA 和蛋白水平。此外,我们发现丹参酮 IIA(TIIA,丹参的主要活性成分之一)治疗可显著降低海水诱导的大鼠、A549 细胞和原代肺泡 II 型细胞中 AQP1 和 AQP5 表达的升高。TIIA 治疗还改善了肺组织病理变化和血气指标,减少了肺水肿和血管渗漏。这些发现表明 AQP1 和 AQP5 可能在肺水肿和肺损伤的发展中起重要作用,而 TIIA 治疗可显著减轻海水暴露引起的 ALI,这可能是通过抑制肺组织中 AQP1 和 AQP5 的过度表达。

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