Quercetin alleviates pulmonary angiogenesis in a rat model of hepatopulmonary syndrome
Rev. bras. pesqui. méd. biol
; Braz. j. med. biol. res;49(7): e5326, 2016. graf
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| ID: biblio-951692
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ABSTRACT
Quercetin shows protective effects against hepatopulmonary syndrome (HPS), as demonstrated in a rat model. However, whether these effects involve pulmonary vascular angiogenesis in HPS remains unclear. Therefore, this study aimed to assess the effect of quercetin on pulmonary vascular angiogenesis and explore the underlying mechanisms. Male Sprague-Dawley rats weighing 200-250 g underwent sham operation or common bile duct ligation (CBDL). Two weeks after surgery, HIF-1α and NFκB levels were assessed in rat lung tissue by immunohistochemistry and western blot. Then, CBDL and sham-operated rats were further divided into 2 subgroups each to receive intraperitoneal administration of quercetin (50 mg/kg daily) or 0.2% Tween for two weeks Sham (Sham+Tween; n=8), CBDL (CBDL+Tween; n=8), Q (Sham+quercetin; n=8), and CBDL+Q (CBDL+quercetin; n=8). After treatment, lung tissue specimens were assessed for protein (immunohistochemistry and western blot) and/or gene expression (quantitative real-time PCR) levels of relevant disease markers, including VEGFA, VEGFR2, Akt/p-Akt, HIF-1α, vWf, and IκB/p-IκB. Finally, arterial blood was analyzed for alveolar arterial oxygen pressure gradient (AaPO2). Two weeks after CBDL, HIF-1α expression in the lung decreased, but was gradually restored at four weeks. Treatment with quercetin did not significantly alter HIF-1α levels, but did reduce AaPO2 as well as lung tissue NF-κB activity, VEGFA gene and protein levels, Akt activity, and angiogenesis. Although hypoxia is an important feature in HPS, our findings suggest that HIF-1α was not the main cause for the VEGFA increase. Interestingly, quercetin inhibited pulmonary vascular angiogenesis in rats with HPS, with involvement of Akt/NF-κB and VEGFA/VEGFR-2 pathways.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Síndrome Hepatopulmonar
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Pulmão
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Neovascularização Patológica
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Antioxidantes
Tipo de estudo:
Evaluation_studies
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Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Braz J Med Biol Res
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Braz. j. med. biol. res
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Braz. j. med. biol. res. (Online)
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Brazilian journal of medical and biological research
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Brazilian journal of medical and biological research (Impresso)
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Rev. bras. pesqui. méd. biol
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Revista brasileira de pesquisas médicas e biológicas
Assunto da revista:
BIOLOGIA
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MEDICINA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Brasil