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Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts

BACKGROUND: Liver transplantation (LT) is currently an effective treatment for end-stage liver disease, but the occurrence of acute rejection (AR) is still the main problem to be solved. The present study aimed to evaluate the effect of gastrodin (GAS) on LT. METHODS: Rat transplant models were esta...

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Autores principales: Yuan, Fangchao, Xu, Xuesong, Wu, Yakun, Duan, Shigang, Wu, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886336/
https://www.ncbi.nlm.nih.gov/pubmed/31828147
http://dx.doi.org/10.1155/2019/9276831
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author Yuan, Fangchao
Xu, Xuesong
Wu, Yakun
Duan, Shigang
Wu, Hao
author_facet Yuan, Fangchao
Xu, Xuesong
Wu, Yakun
Duan, Shigang
Wu, Hao
author_sort Yuan, Fangchao
collection PubMed
description BACKGROUND: Liver transplantation (LT) is currently an effective treatment for end-stage liver disease, but the occurrence of acute rejection (AR) is still the main problem to be solved. The present study aimed to evaluate the effect of gastrodin (GAS) on LT. METHODS: Rat transplant models were established and divided into SHAM, LT, GAS-L (50 mg/kg GAS), and GAS-H (100 mg/kg GAS) groups. The liver function, inflammatory factors, liver histopathology, survival of rats, number of M2-type macrophages, liver cell apoptosis, and pathway proteins were assayed at 7 days and 14 days after the operations. RESULTS: With increasing GAS concentrations, liver function, expression of proinflammatory factors in the liver, and expression of M2-type molecules in macrophages were significantly improved, and the survival time of rats was significantly prolonged (P < 0.05). All rats treated with low or high doses of GAS were judged to have nondeterministic acute rejection. Flow cytometry showed that liver cell apoptosis was decreased significantly in the GAS-L and GAS-H groups after GAS administration compared with apoptosis and differentiation in the LT group (P < 0.05). Expression levels of Caspase-3, Bad, and Bax proteins were decreased, and the expression of the antiapoptotic protein Bcl-2 was increased in the GAS-L and GAS-H groups (P < 0.05). Mechanistically, the ERS-related IRE1α/TRAF2/NF-κB pathway was suppressed by GAS, and GAS acted mainly on intrahepatic macrophages to affect AR and reduce ROS production (P < 0.05). CONCLUSION: GAS ameliorated AR by inhibiting the IRE1α/TRAF2/NF-κB pathway in LT.
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spelling pubmed-68863362019-12-11 Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts Yuan, Fangchao Xu, Xuesong Wu, Yakun Duan, Shigang Wu, Hao Biomed Res Int Research Article BACKGROUND: Liver transplantation (LT) is currently an effective treatment for end-stage liver disease, but the occurrence of acute rejection (AR) is still the main problem to be solved. The present study aimed to evaluate the effect of gastrodin (GAS) on LT. METHODS: Rat transplant models were established and divided into SHAM, LT, GAS-L (50 mg/kg GAS), and GAS-H (100 mg/kg GAS) groups. The liver function, inflammatory factors, liver histopathology, survival of rats, number of M2-type macrophages, liver cell apoptosis, and pathway proteins were assayed at 7 days and 14 days after the operations. RESULTS: With increasing GAS concentrations, liver function, expression of proinflammatory factors in the liver, and expression of M2-type molecules in macrophages were significantly improved, and the survival time of rats was significantly prolonged (P < 0.05). All rats treated with low or high doses of GAS were judged to have nondeterministic acute rejection. Flow cytometry showed that liver cell apoptosis was decreased significantly in the GAS-L and GAS-H groups after GAS administration compared with apoptosis and differentiation in the LT group (P < 0.05). Expression levels of Caspase-3, Bad, and Bax proteins were decreased, and the expression of the antiapoptotic protein Bcl-2 was increased in the GAS-L and GAS-H groups (P < 0.05). Mechanistically, the ERS-related IRE1α/TRAF2/NF-κB pathway was suppressed by GAS, and GAS acted mainly on intrahepatic macrophages to affect AR and reduce ROS production (P < 0.05). CONCLUSION: GAS ameliorated AR by inhibiting the IRE1α/TRAF2/NF-κB pathway in LT. Hindawi 2019-11-20 /pmc/articles/PMC6886336/ /pubmed/31828147 http://dx.doi.org/10.1155/2019/9276831 Text en Copyright © 2019 Fangchao Yuan et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yuan, Fangchao
Xu, Xuesong
Wu, Yakun
Duan, Shigang
Wu, Hao
Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts
title Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts
title_full Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts
title_fullStr Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts
title_full_unstemmed Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts
title_short Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts
title_sort gastrodin ameliorates acute rejection via ire1α/traf2/nf-κb in rats receiving liver allografts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886336/
https://www.ncbi.nlm.nih.gov/pubmed/31828147
http://dx.doi.org/10.1155/2019/9276831
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