中国普外基础与临床杂志

中国普外基础与临床杂志

ALPPS 动物模型及其基础研究进展

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目的 了解联合肝脏分隔和门静脉结扎的二步肝切除术(ALPPS)动物模型及其基础研究的最新进展,为 ALPPS 的基础研究和临床应用提供新的思路。 方法 收集有关 ALPPS 的基础研究和动物模型的相关文献进行分析并作综述。 结果 至 2018 年 3 月,国内外公开报道的 ALPPS 动物模型相关文献共计 19 篇,其中大鼠模型 11 篇,小鼠模型 4 篇,猪模型 2 篇,兔模型 1 篇,羊模型 1 篇。文献以正常肝背景下模拟的 ALPPS 手术为主(16 篇),其他包括结直肠肝转移小鼠 ALPPS 模型 2 篇,肝硬变背景下的 ALPPS 动物模型仅有 1 篇中文文献报道。ALPPS 建模时,门静脉分支的结扎比例为 50%~90%,根据缺血线及肝脏韧带来定位和分割肝脏,断面多以缝扎、电凝等方式止血。以上动物模型在术后均能观察到剩余肝组织增生,增生的主要原因:一是来于细胞因子,如肝细胞生长因子(HGF)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)等参与诱导肝细胞增殖相关基因表达的上调,二是剩余肝的门静脉及肝动脉血流增加,加速了肝脏细胞增殖。 结论 动物模型是研究 ALPPS 手术安全性及术后肝脏增生机制的主要工具,但涉及伴有肝硬变背景的肝脏肿瘤模型的研究仍较少。ALPPS 术后肝脏再生的机制仍处于探索中,还需要更多的基础实验和临床病例来进一步研究。

Objective To understand the advances in animal model and basic research of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), and to provide new ideas for basic research and clinical application of ALPPS. Methods The literatures on the basic research and animal models of ALPPS were analyzed and reviewed. Results By March 2018, there were 19 articles related to ALPPS animal models published, including 11 rat model articles, 4 mouse model articles, 2 pig model articles, 1 rabbit model article, and 1 sheep model article. These models of ALPPS were mainly simulated in normal liver background (16 articles), only 2 mouse model of colorectal liver metastasis and 1 rat model of ALPPS under the sclerotic liver background on Chinese article. In cases of rat’s models, portal blood flow deprivation of 50%–90% was finished by portal vein ligation, and the liver was localized and segmented according to the ischemic line and the ligaments of the liver, and the liver partition was mostly sutured and electrocoagulated to stop bleeding. In the above models, remnant liver hyperplasia was observed after surgery. The main causes of hyperplasia were serum cytokines [hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and so on.]-mediated enhancement of proliferative gene expression, and secondly preservation of the portal vein lobes to increase blood volume and to accelerate liver proliferation. Conclusions The animal model is the main tool to study the safety of ALPPS and liver regeneration, but there are still few studies in the models with liver cirrhosis and liver tumors. The mechanism of liver regeneration after ALPPS is still unclear, and more basic experiments and clinical cases are needed for further study.

关键词: 联合肝脏分隔和门静脉结扎的二步肝切除术; 动物模型; 肝硬变; 再生; 综述

Key words: associating liver partition and portal vein ligation for staged hepatectomy; animal model; cirrhosis; regeneration; review

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