Tzirogiannis Konstantinos N, Kourentzi Kalliopi T, Zyga Sofia, Papalimneou Vassiliki, Tsironi Maria, Grypioti Agni D, Protopsaltis Ioannis, Panidis Dimitrios, Panoutsopoulos Georgios I
Department of Experimental Pharmacology, Medical School, Athens University, Athens, 11527, Greece.
Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, 23100, Greece.
BMC Gastroenterol. 2014 Nov 30;14:201. doi: 10.1186/s12876-014-0201-2.
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.
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 [(3)H]-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.
Liver regeneration peaked at 24 h ([(3)H]-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 ([(3)H]-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.
In conclusion, 5-HT7 receptor is a novel type of serotonin receptor implicated in hepatocyte proliferation.
血清素具有广泛的作用，包括细胞增殖和分化。血清素作为一种不完全有丝分裂原，对肝脏再生的影响最近已被揭示，且是通过5 - HT2受体介导的。本研究的目的是探讨5 - HT7受体阻断对部分肝切除术后肝脏再生的影响。
对雄性Wistar大鼠进行60 - 70%的部分肝切除术。在部分肝切除术前2小时和术后16小时，通过腹腔注射盐酸SB - 269970进行5 - HT7受体阻断，并在部分肝切除术后16小时通过腹腔注射SB - 258719进行5 - HT7受体阻断。在部分肝切除术后直至72小时的不同时间点处死动物。通过将[³H] - 胸腺嘧啶掺入肝DNA、苏木精 - 伊红（HE）切片中的有丝分裂指数以及通过免疫化学检测Ki67核抗原来评估肝脏再生。通过腹腔注射AS - 19来逆转5 - HT7阻断。还对血清和肝组织脂质进行了定量分析。
在对照组大鼠中，肝脏再生在24小时（通过免疫化学检测Ki67将[³H] - 胸腺嘧啶掺入肝DNA和有丝分裂指数）和32小时（HE切片中的有丝分裂指数）达到峰值。在部分肝切除术前2小时应用5 - HT7受体阻断对肝脏再生没有影响。当在部分肝切除术后16小时应用5 - HT7受体阻断（通过SB - 258719和SB - 269970）时，肝脏再生大大减弱，并在部分肝切除术后32小时（通过免疫化学检测Ki67将[³H] - 胸腺嘧啶掺入肝DNA和有丝分裂指数）和40小时（HE切片中的有丝分裂指数）达到峰值。AS - 19给药完全逆转了观察到的肝脏再生减弱。
总之，5 - HT7受体是一种涉及肝细胞增殖的新型血清素受体。
