title: Quercetin alleviates pulmonary angiogenesis in a rat model of hepatopulmonary syndrome.
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.
authors.affiliation: Department of Physiology, Changzhi Medical College, Changzhi, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Microbiology, Changzhi Medical College, Changzhi, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Functional Laboratory of Changzhi Medical College, Changzhi, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Physiology, Changzhi Medical College, Changzhi, China.
authors.forename: G
authors.initials: G
authors.lastname: Shang
authors.affiliation: Department of Physiology, Changzhi Medical College, Changzhi, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Liver Disease Institute of Changzhi Medical College, Changzhi, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Changzhi Medical College, Changzhi, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: A
authors.initials: A
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis; D015153:Blotting, Western; D003135:Common Bile Duct / Q000601:surgery; D004195:Disease Models, Animal; D020065:Hepatopulmonary Syndrome / Q000188:drug therapy* / Q000473:pathology; D007150:Immunohistochemistry; D008026:Ligation; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000032:analysis; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D011794:Quercetin / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000187:drug effects; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000975:Antioxidants; D051792:Basic Helix-Loop-Helix Proteins; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D011794:Quercetin; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099162:Endothelial PAS Domain-Containing Protein 1; C467498:vascular endothelial growth factor A, rat; C000602029:Kdr protein, rat