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Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation

Ischemia/reperfusion (I/R) injury can occur during small-for-size liver transplantation, resulting in delayed graft function and decreased long-term graft survival. The aim of the present study was to evaluate the effects of genetic overexpression of endothelial nitric oxide synthase (eNOS) in prote...

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Autores principales: Zhang, Bo, Liu, Qiu-Hua, Zhou, Cui-Jie, Hu, Ming-Zheng, Qian, Hai-Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103764/
https://www.ncbi.nlm.nih.gov/pubmed/27882135
http://dx.doi.org/10.3892/etm.2016.3762
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author Zhang, Bo
Liu, Qiu-Hua
Zhou, Cui-Jie
Hu, Ming-Zheng
Qian, Hai-Xin
author_facet Zhang, Bo
Liu, Qiu-Hua
Zhou, Cui-Jie
Hu, Ming-Zheng
Qian, Hai-Xin
author_sort Zhang, Bo
collection PubMed
description Ischemia/reperfusion (I/R) injury can occur during small-for-size liver transplantation, resulting in delayed graft function and decreased long-term graft survival. The aim of the present study was to evaluate the effects of genetic overexpression of endothelial nitric oxide synthase (eNOS) in protecting hepatocytes against I/R injury in a rat model of small-for-size liver transplantation. L02 liver cells were transfected with the eNOS gene using an adenovirus (Ad-eNOS). eNOS expression was detected using quantitative polymerase chain reaction and western blot analysis. To evaluate the effect of eNOS overexpression, L02 cells were placed in a hypoxic environment for 12 h and immediately transferred to an oxygen-enriched atmosphere. For in vivo testing, rats pretreated with Ad-eNOS or control underwent small-for-size liver transplantation. At 6 h after reperfusion, the bile quantity, serum transaminase and nitric oxide (NO) levels, and histological outcomes were evaluated. Cell apoptosis was assessed by flow cytometry or TUNEL assay. In vitro, Ad-eNOS prevented apoptosis in L02 cells with an increase in the level of NO in culture supernatant. In vivo, Ad-eNOS pre-treatment significantly increased bile production, improved abnormal transaminase levels, diminished apoptosis among liver cells, and decreased hepatocellular damage at 6 h after I/R injury. The eNOS-mediated renal protective effects might be associated with the downregulation of tumor necrosis factor-α and a reduction in macrophage activation in the early stage of reperfusion in small-for-size liver allografts. eNOS-derived NO production significantly attenuates hepatic I/R injury. Thus, eNOS overexpression constitutes a promising therapeutic approach to prevent liver I/R injury following small-for-size liver transplantation.
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spelling pubmed-51037642016-11-23 Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation Zhang, Bo Liu, Qiu-Hua Zhou, Cui-Jie Hu, Ming-Zheng Qian, Hai-Xin Exp Ther Med Articles Ischemia/reperfusion (I/R) injury can occur during small-for-size liver transplantation, resulting in delayed graft function and decreased long-term graft survival. The aim of the present study was to evaluate the effects of genetic overexpression of endothelial nitric oxide synthase (eNOS) in protecting hepatocytes against I/R injury in a rat model of small-for-size liver transplantation. L02 liver cells were transfected with the eNOS gene using an adenovirus (Ad-eNOS). eNOS expression was detected using quantitative polymerase chain reaction and western blot analysis. To evaluate the effect of eNOS overexpression, L02 cells were placed in a hypoxic environment for 12 h and immediately transferred to an oxygen-enriched atmosphere. For in vivo testing, rats pretreated with Ad-eNOS or control underwent small-for-size liver transplantation. At 6 h after reperfusion, the bile quantity, serum transaminase and nitric oxide (NO) levels, and histological outcomes were evaluated. Cell apoptosis was assessed by flow cytometry or TUNEL assay. In vitro, Ad-eNOS prevented apoptosis in L02 cells with an increase in the level of NO in culture supernatant. In vivo, Ad-eNOS pre-treatment significantly increased bile production, improved abnormal transaminase levels, diminished apoptosis among liver cells, and decreased hepatocellular damage at 6 h after I/R injury. The eNOS-mediated renal protective effects might be associated with the downregulation of tumor necrosis factor-α and a reduction in macrophage activation in the early stage of reperfusion in small-for-size liver allografts. eNOS-derived NO production significantly attenuates hepatic I/R injury. Thus, eNOS overexpression constitutes a promising therapeutic approach to prevent liver I/R injury following small-for-size liver transplantation. D.A. Spandidos 2016-11 2016-09-30 /pmc/articles/PMC5103764/ /pubmed/27882135 http://dx.doi.org/10.3892/etm.2016.3762 Text en Copyright: © Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhang, Bo
Liu, Qiu-Hua
Zhou, Cui-Jie
Hu, Ming-Zheng
Qian, Hai-Xin
Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation
title Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation
title_full Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation
title_fullStr Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation
title_full_unstemmed Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation
title_short Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation
title_sort protective effect of enos overexpression against ischemia/reperfusion injury in small-for-size liver transplantation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103764/
https://www.ncbi.nlm.nih.gov/pubmed/27882135
http://dx.doi.org/10.3892/etm.2016.3762
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