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The Beneficial Effects of P2X(7) Antagonism in Rats with Bile Duct Ligation-induced Cirrhosis
Splanchnic angiogenesis in liver cirrhosis often leads to complications as gastroesophageal variceal hemorrhage and the treatment efficacy is adversely affected by poor portal-systemic collateral vasoresponsiveness related to nitric oxide (NO). Purinergic receptor subtype P2X(7) participates in the...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416718/ https://www.ncbi.nlm.nih.gov/pubmed/25933224 http://dx.doi.org/10.1371/journal.pone.0124654 |
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author | Tung, Hung-Chun Lee, Fa-Yauh Wang, Sun-Sang Tsai, Ming-Hung Lee, Jing-Yi Huo, Teh-Ia Huang, Hui-Chun Chuang, Chiao-Lin Lin, Han-Chieh Lee, Shou-Dong |
author_facet | Tung, Hung-Chun Lee, Fa-Yauh Wang, Sun-Sang Tsai, Ming-Hung Lee, Jing-Yi Huo, Teh-Ia Huang, Hui-Chun Chuang, Chiao-Lin Lin, Han-Chieh Lee, Shou-Dong |
author_sort | Tung, Hung-Chun |
collection | PubMed |
description | Splanchnic angiogenesis in liver cirrhosis often leads to complications as gastroesophageal variceal hemorrhage and the treatment efficacy is adversely affected by poor portal-systemic collateral vasoresponsiveness related to nitric oxide (NO). Purinergic receptor subtype P2X(7) participates in the modulation of inflammation, angiogenesis, fibrogenesis and vasoresponsiveness, but the relevant influence in cirrhosis is unknown. Common bile duct-ligated (CBDL) or sham-operated Spraque-Dawley rats received brilliant blue G (BBG, a P2X(7) antagonist and food additive) or vehicle from the 15(th) to 28(th) day after operations, then hemodynamics, mesenteric angiogenesis, portal-systemic shunting, liver fibrosis, and protein expressions of angiogenic and fibrogenic factors were evaluated. The influence of oxidized ATP (oATP, another P2X(7) receptor antagonist) on the collateral vasoresponsiveness to arginine vasopressin (AVP) was also surveyed. BBG decreased superior mesenteric artery (SMA) flow, portal-systemic shunting, mesenteric vascular density, and mesenteric protein expressions of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), phospho (p)-VEGFR2, platelet-derived growth factor (PDGF), PDGF receptor beta (PDGFRβ), cyclooxygenase (COX)-1, COX-2, and endothelial NO synthase (eNOS) in CBDL rats. BBG also ameliorated liver fibrosis and down-regulated hepatic interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), PDGF, IL-1β, transforming growth factor-beta (TGF-β), p-extracellular-signal-regulated kinases (ERK), and alpha-smooth muscle actin (α-SMA) expressions in CBDL rats. The collateral vasocontractility to AVP was enhanced by oATP. oATP down-regulated eNOS, inducible NOS (iNOS), VEGF, Akt, p-Akt, and nuclear factor-kappa B (NF-κB) expressions in splenorenal shunt, the most prominent intra-abdominal collateral vessel in rodents. P2X(7) antagonism alleviates splanchnic hyperemia, severity of portal-systemic shunting, mesenteric angiogenesis, liver fibrosis, and enhances portal-systemic collateral vasoresponsiveness in cirrhotic rats. P2X(7) blockade may be a feasible strategy to control cirrhosis and complications. |
format | Online Article Text |
id | pubmed-4416718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44167182015-05-07 The Beneficial Effects of P2X(7) Antagonism in Rats with Bile Duct Ligation-induced Cirrhosis Tung, Hung-Chun Lee, Fa-Yauh Wang, Sun-Sang Tsai, Ming-Hung Lee, Jing-Yi Huo, Teh-Ia Huang, Hui-Chun Chuang, Chiao-Lin Lin, Han-Chieh Lee, Shou-Dong PLoS One Research Article Splanchnic angiogenesis in liver cirrhosis often leads to complications as gastroesophageal variceal hemorrhage and the treatment efficacy is adversely affected by poor portal-systemic collateral vasoresponsiveness related to nitric oxide (NO). Purinergic receptor subtype P2X(7) participates in the modulation of inflammation, angiogenesis, fibrogenesis and vasoresponsiveness, but the relevant influence in cirrhosis is unknown. Common bile duct-ligated (CBDL) or sham-operated Spraque-Dawley rats received brilliant blue G (BBG, a P2X(7) antagonist and food additive) or vehicle from the 15(th) to 28(th) day after operations, then hemodynamics, mesenteric angiogenesis, portal-systemic shunting, liver fibrosis, and protein expressions of angiogenic and fibrogenic factors were evaluated. The influence of oxidized ATP (oATP, another P2X(7) receptor antagonist) on the collateral vasoresponsiveness to arginine vasopressin (AVP) was also surveyed. BBG decreased superior mesenteric artery (SMA) flow, portal-systemic shunting, mesenteric vascular density, and mesenteric protein expressions of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), phospho (p)-VEGFR2, platelet-derived growth factor (PDGF), PDGF receptor beta (PDGFRβ), cyclooxygenase (COX)-1, COX-2, and endothelial NO synthase (eNOS) in CBDL rats. BBG also ameliorated liver fibrosis and down-regulated hepatic interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), PDGF, IL-1β, transforming growth factor-beta (TGF-β), p-extracellular-signal-regulated kinases (ERK), and alpha-smooth muscle actin (α-SMA) expressions in CBDL rats. The collateral vasocontractility to AVP was enhanced by oATP. oATP down-regulated eNOS, inducible NOS (iNOS), VEGF, Akt, p-Akt, and nuclear factor-kappa B (NF-κB) expressions in splenorenal shunt, the most prominent intra-abdominal collateral vessel in rodents. P2X(7) antagonism alleviates splanchnic hyperemia, severity of portal-systemic shunting, mesenteric angiogenesis, liver fibrosis, and enhances portal-systemic collateral vasoresponsiveness in cirrhotic rats. P2X(7) blockade may be a feasible strategy to control cirrhosis and complications. Public Library of Science 2015-05-01 /pmc/articles/PMC4416718/ /pubmed/25933224 http://dx.doi.org/10.1371/journal.pone.0124654 Text en © 2015 Tung et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Tung, Hung-Chun Lee, Fa-Yauh Wang, Sun-Sang Tsai, Ming-Hung Lee, Jing-Yi Huo, Teh-Ia Huang, Hui-Chun Chuang, Chiao-Lin Lin, Han-Chieh Lee, Shou-Dong The Beneficial Effects of P2X(7) Antagonism in Rats with Bile Duct Ligation-induced Cirrhosis |
title | The Beneficial Effects of P2X(7) Antagonism in Rats with Bile Duct Ligation-induced Cirrhosis |
title_full | The Beneficial Effects of P2X(7) Antagonism in Rats with Bile Duct Ligation-induced Cirrhosis |
title_fullStr | The Beneficial Effects of P2X(7) Antagonism in Rats with Bile Duct Ligation-induced Cirrhosis |
title_full_unstemmed | The Beneficial Effects of P2X(7) Antagonism in Rats with Bile Duct Ligation-induced Cirrhosis |
title_short | The Beneficial Effects of P2X(7) Antagonism in Rats with Bile Duct Ligation-induced Cirrhosis |
title_sort | beneficial effects of p2x(7) antagonism in rats with bile duct ligation-induced cirrhosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416718/ https://www.ncbi.nlm.nih.gov/pubmed/25933224 http://dx.doi.org/10.1371/journal.pone.0124654 |
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