Effect of 5-HT7receptor blockade on liver regeneration after 60-70% partial hepatectomy

BMC Gastroenterology

Research Article

Agni D Grypioti¹  Konstantinos N Tzirogiannis¹  Kalliopi T Kourentzi¹  Vassiliki Papalimneou²  Ioannis Protopsaltis³  Maria Tsironi⁴  Sofia Zyga⁴  Dimitrios Panidis⁴  Georgios I Panoutsopoulos⁵ 

[1] Department of Experimental Pharmacology, Medical School, Athens University, 11527, Athens, Greece;Department of Internal Medicine, Elpis General Hospital, 11522, Athens, Greece;Department of Internal Medicine, Tzanio General Hospital of Piraeus, 18537, Piraeus, Greece;Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, 23100, Sparta, Greece;Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Orthias Artemidos and Plateon, 23100, Sparta, Greece;

关键词: Liver regeneration;    Partial hepatectomy;    5-HT7 receptor;    SB-269970;    SB-258719;    AS-19;   

DOI  :  10.1186/s12876-014-0201-2

 received in 2014-02-28, accepted in 2014-11-11,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundSerotonin exhibits a vast repertoire of actions including cell proliferation and differentiation. The effect of serotonin, as an incomplete mitogen, on liver regeneration has recently been unveiled and is mediated through 5-HT2 receptor. The aim of the present study was to investigate the effect of 5-HT7 receptor blockade on liver regeneration after partial hepatectomy.MethodsMale Wistar rats were subjected to 60-70% partial hepatectomy. 5-HT7 receptor blockade was applied by intraperitoneal administration of SB-269970 hydrochloride two hours prior to and sixteen hours after partial hepatectomy and by intraperitoneal administration of SB-258719 sixteen hours after partial hepatectomy. Animals were sacrificed at different time points until 72 h after partial hepatectomy. Liver regeneration was evaluated by [3H]-thymidine incorporation into hepatic DNA, the mitotic index in hematoxylin-eosin (HE) sections and by immunochemical detection of Ki67 nuclear antigen. Reversion of 5-HT7 blockade was performed by intraperitoneal administration of AS-19. Serum and liver tissue lipids were also quantified.ResultsLiver regeneration peaked at 24 h ([3H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and at 32 h (mitotic index in HE sections) in the control group of rats. 5-HT7 receptor blockade had no effect on liver regeneration when applied 2 h prior to partial hepatectomy. Liver regeneration was greatly attenuated when blockade of 5-HT7 receptor was applied (by SB-258719 and SB-269970) at 16 h after partial hepatectomy and peaked at 32 h ([3H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and 40 h (mitotic index in HE sections) after partial hepatectomy. AS-19 administration totally reversed the observed attenuation of liver regeneration.ConclusionsIn conclusion, 5-HT7 receptor is a novel type of serotonin receptor implicated in hepatocyte proliferation.

【 授权许可】

Unknown   
© Tzirogiannis et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.