Down-regulated expression of AQP5 on lung in rat DIC model induced by LPS and its effect on the development of pulmonary edema

Down-regulated expression of AQP5 on lung in rat DIC model induced by LPS and its effect on the development of pulmonary edema
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DOI:
10.1016/j.pupt.2013.03.013
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发表时间:
2013-12-01
影响因子:
3.2
通讯作者:
Xin, Xiaomin
Xin, Xiaomin
中科院分区:
医学3区
文献类型:
--
作者:
Jin, Yingyu;Yu, Guangzhe;Xin, Xiaomin

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弥散性血管内凝血(DIC)是一种以广泛凝血激活为特征的获得性综合征,可导致机体多器官功能衰竭。脂多糖(LPS)诱导的大鼠DIC与继发性肺水肿有关。肺组织具有高度的透水性,并表达多种水通道蛋白(AQP)。因此,我们探讨是否AQP 5参与LPS诱导的肺水肿的发病机制。LPS(30 mg/kg)静脉注射4、6、8、10、12 h,诱导DIC。测定血小板计数(PLT)、D-二聚体(DD)、纤维蛋白原(FIB)、凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)。采用实时定量PCR和Western blot方法检测AQP 5的mRNA和蛋白表达。肺样本用苏木精-伊红染色,并测量肺湿/干重(W/D)比。结果显示,LPS致肺损伤后4 ~ 12 h,PLT、FIB显著降低,DD、PT、APTT显著升高,肺组织出现微血栓,同时AQP 5表达下调。LPS灌注后6 ~ 12 h,肺组织病理学改变如肺水肿、肺湿重/干重比增加。提示AQP 5表达降低可能导致肺泡-毛细血管间液体转运障碍,为揭示DIC大鼠肺水肿的发病机制提供了AQP 5基因调控的报道。(C)2013爱思唯尔有限公司版权所有。
Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by the widespread activation of coagulation, which leads to failure of multiple organs in the body. DIC of rat with lipopolysaccharide (LPS) is associated with subsequent pulmonary edema. Lung tissue is highly water permeable and expresses several aquaporins (AQPs). We therefore explored whether AQP5 involved in the pathogenesis of LPS-induced lung edema. The rats were intravenously infused with LPS (30 mg/kg) for 4 h, 6 h, 8 h, 10 h, and 12 h to induce DIC. Platelets count (PLT), D-Dimer (DD), fibrinogen (FIB), prothrombin time (PT), and activated partial thromboplastin time (APTT) were determined. Real-time quantitative PCR and Western blot were used to analyze the mRNA and protein expression of AQP5. Lung samples were stained with hematoxylin-eosin and lung wet/dry weight (W/D) ratios were measured. Here, we demonstrated that PLT and FIB values were significant decreased, the values for DD, PT, and APTT were marked increased, microthrombus was observed in lung specimens, and simultaneously with the AQP5 showed down-regulated expression following LPS infused from 4 h to 12 h. However, histopathological changes such as pulmonary edema and the increased lung W/D weight ratio were observed after LPS infused from 6 h to 12 h. These results indicated that the decreased expression of AQP5 maybe induce liquid transport obstacles between alveolar and capillary, and provides the report of AQP5 gene regulation, revealing the pathogenesis of pulmonary edema in DIC model of rat. (C) 2013 Elsevier Ltd. All rights reserved.