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Caspase-3 inhibition prevents the development of hepatopulmonary syndrome in CBDL rats by alleviating pulmonary injury.
MedLine Citation:
PMID:  25113058     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND AND AIMS: Common bile duct ligation (CBDL) rats is an accepted experimental model of hepatopulmonary syndrome (HPS), defined as liver disease and intrapulmonary vascular dilatation and hypoxemia. Pulmonary Akt and ERK activation, followed by angiogenesis in the later stages of CBDL, contribute to the pathogenesis of HPS. However, the mechanisms behind Akt and ERK activation remain undefined. Pulmonary injury induced by increased bilirubin, endotoxin and inflammatory mediators occurs in the early stages of CBDL. We assessed the effects of relieving pulmonary injury on Akt and ERK activation and on the development of HPS following CBDL.
METHODS: Pulmonary injury, angiogenesis, arterial oxygenation, cell proliferation and, phospho-Akt and ERK1 were evaluated in CBDL animals with or without caspase-3 inhibition (Z-DEVD-FMK). Pulmonary injury was assessed by histology and quantifying apoptosis and AQP1 levels. Lung angiogenesis was assessed by quantifying AQP1 level, vWF-positive cells and microvessel count.
RESULTS: Pulmonary apoptosis and caspase-3 activation were markedly increased in the early stages of CBDL. Caspase-3 inhibition alleviated apoptosis, the reduction in AQP1, phospho-Akt and ERK1 levels, and pulmonary injury 1 week after CBDL. Caspase-3 inhibition also reduced AQP1, phospho-Akt and ERK1 levels, vWF-positive cells, cell proliferation, microvessel count, and microvascular dilatation, and improved arterial oxygenation 3 weeks following CBDL.
CONCLUSIONS: Caspase-3 inhibition alleviates pulmonary injury, thereby preventing angiogenesis as well as the development of HPS in CBDL rats. These effects are related to the regulation of the Akt and ERK1 pathways. This article is protected by copyright. All rights reserved.
Authors:
Bing Chen; Jiaolin Ning; Jianteng Gu; Jian Cui; Yong Yang; Zhi Wang; Jing Zeng; Bin Yi; Kaizhi Lu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-11
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  -     ISSN:  1478-3231     ISO Abbreviation:  Liver Int.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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