Effect of 5-HT7 receptor blockade on liver regeneration after 60-70% partial hepatectomy

BMC Gastroenterology

Georgios I Panoutsopoulos²  Dimitrios Panidis³  Ioannis Protopsaltis⁴  Agni D Grypioti⁵  Maria Tsironi³  Vassiliki Papalimneou¹  Sofia Zyga³  Kalliopi T Kourentzi⁵  Konstantinos N Tzirogiannis⁵ 

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

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

Others  :  1121750
DOI  :  10.1186/s12876-014-0201-2

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

【 摘 要 】

Background

Serotonin 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.

Methods

Male 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.

Results

Liver 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.

Conclusions

In conclusion, 5-HT₇ receptor is a novel type of serotonin receptor implicated in hepatocyte proliferation.

【 授权许可】

   
2014 Tzirogiannis et al.; licensee BioMed Central Ltd.

【 图 表 】

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