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

Tanshinone IIA ameliorates seawater exposure-induced lung injury by inhibiting aquaporins (AQP) 1 and AQP5 expression in lung
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DOI:
10.1016/j.resp.2011.01.005
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发表时间:
2011-04-30
影响因子:
2.3
通讯作者:
Li, Zhichao
Li, Zhichao
中科院分区:
医学4区
文献类型:
--
作者:
Li, Jiahuan;Xu, Min;Li, Zhichao

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水通道蛋白(Aquaporins,AQPs)是一类跨膜水通道,介导对体液容量和渗透压变化的生理反应。目前尚不清楚AQPs在海水淹溺性急性肺损伤(ALI)中的作用,以及AQPs的药理调节能否减轻海水吸入所致ALI的严重程度。在我们的研究中,RT-PCR和Western blotting的结果表明,气管内安装海水上调了肺组织中AQP1和AQP5的mRNA和蛋白水平。此外,我们还发现丹参酮IIA(丹参酮IIA)能显著降低海水诱导的大鼠、A549细胞和原代肺泡II型细胞AQP1和AQP5的表达。改善肺组织病理改变和血气指标,减轻肺水肿和血管渗漏。提示AQP1和AQP5可能在肺水肿和肺损伤的发生发展过程中起重要作用,TIIA可明显减轻海水暴露所致的ALI,其机制可能是通过抑制AQP1和AQP5在肺组织的过度表达而实现的。(C)2011爱思唯尔B.V.保留所有权利。
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. (C) 2011 Elsevier B.V. All rights reserved.