Effect of portal hemodynamics on liver regeneration studied in a novel portohepatic shunt rat model
Effect of portal hemodynamics on liver regeneration studied in a novel portohepatic shunt rat model
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DOI：
10.1016/j.surg.2004.03.012
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发表时间：
2004-11-01
期刊：
影响因子：
3.8
通讯作者：
Monden, M
中科院分区：
文献类型：
--
作者：
Marubashi, S;Sakon, M;Monden, M
背景资料。肝部分切除后，门静脉血流动力学在肝再生中的作用尚不完全清楚。我们研究的目的是利用一种新的大鼠模型来表征门静脉血流动力学的影响。我们建立了一种70%肝切除的门肝分流大鼠模型(PHS模型)，在该模型中，门静脉压力在70%肝切除期间和之后保持稳定。为了评估门静脉血流动力学在前24小时内对肝脏损伤和再生的影响，我们将PHS大鼠与单纯70%肝切除的大鼠进行了比较。两组的生化和组织病理学改变相似。对照组肝脏重量增加，而PHS组肝脏重量没有增加(P=0.0021)。对照组肝细胞增大，但PHS组肝细胞未见增大，尽管两组肝细胞DNA合成相似。24小时后，PHS组肝细胞凋亡率显著增加，而对照组在整个研究过程中观察到极少量的细胞凋亡。肝细胞生长因子升高与正常对照组相似，不同之处在于肝细胞生长因子未被激活。我们的结果提示，70%肝切除后早期门静脉高动力状态是肝再生所必需的，它通过激活肝细胞生长因子，促进肝细胞肥大，避免细胞凋亡，而肝细胞DNA合成与门静脉血流动力学无关。
Background. The role of portal hemodynamics on liver regeneration, after partial hepatectomy is not fully understood. The aim of our study was to characterize the effects of Portal hemodynamics using a novel rat model.Methods. We established a rat model of a portohepatic shunt with a 70% hepatectomy (PHS model), in which the portal pressure remained stable during and after the 70% hepatectomy. To assess the effect of portal hemodynamics on liver injury and regeneration in the first 24 hours, we compared PHS rats with those with a simple 70% hepatectomy.Results. Biochemical and histopathologic changes were similar between the 2 groups. Liver weight increased in the control, whereas it did not in the PHS group (P = .0021). Hepatocytes were enlarged in the control but not in the PHS group, although DNA synthesis was similar in both groups. Apoptotic hepatocytes increased markedly in PHS at 24 hours, whereas minimal apoptosis was noted throughout the course of the study in the control group. Hepatocyte growth factor increased similarly, except that it was not activated in PHS.Conclusions. Our results suggested that a portal hyperdynamic state early after a 70 % hepatectomy was necessary for liver regeneration through activation of hepatocyte growth factor, Promoting hepatocyte hypertrophy and avoiding apoptosis, while DNA synthesis in hepatocytes was independent of portal hemodynamics.