Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation
Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation
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DOI：
10.1111/j.1365-2613.2008.00597.x
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发表时间：
2008-08-01
影响因子：
3
通讯作者：
Colle, Isabelle
中科院分区：
文献类型：
--
作者：
Geerts, Anja M.;Vanheule, Eline;Colle, Isabelle
门静脉高压（PHT）小鼠模型的表征在文献中缺乏。因此，本研究的目的是对两种肝硬化合并PHT模型和一种孤立PHT模型在PHT发展过程中的组织学方法进行比较。采用部分门静脉结扎术（PPVL）建立离体PHT模型。采用胆总管结扎（CBDL）或皮下注射四氯化碳（CCl4）（每周2次，1 ml/kg）建立2只门脉高压肝硬化小鼠模型。这些模型分别代表继发性胆汁性肝硬化和酒精性肝硬化。在不同时间点处死小鼠，用组织学和超微结构方法评价肝脏的变化。与门静脉压力测量有相关性。组织学显示PPVL小鼠无纤维化或肝硬化。他们患上了孤立性门静脉高压症。CBDL诱导后，小鼠在6周后出现肝硬化特征，同时门静脉压力增加。在那个时间点，50%的老鼠有腹水。给予CCl4 16周后，发现肝脏微结节性肝硬化与门静脉高压症相关。这是首次在小鼠中对三种广泛使用的动物模型进行描述性研究，从而可以研究肝硬化和门静脉高压症的病理生理变化。小鼠PPVL导致孤立性门静脉高压症模型。50%发生腹水的小鼠在胆总管结扎6周后发生继发性胆汁性肝硬化。皮下注射CCl4 16周可诱发肝硬化和门脉高压，无腹水。此外，本研究首次描述了通过皮下注射CCl4建立的小鼠肝硬化模型。描述良好的小鼠模型将有助于基因敲除或转基因小鼠的使用，并有助于更好地理解门脉高压和肝硬化领域的潜在分子途径。
The characterization of mice models of portal hypertension (PHT) is lacking in the literature. Therefore, the aim of the present study was to make a histological approach during development of PHT in two models of cirrhosis with PHT compared with one model of isolated PHT. The model of isolated PHT was developed by partial portal vein ligation (PPVL). Two portal hypertensive cirrhotic mice models were developed either by common bile duct ligation (CBDL) or administration of carbon tetrachloride (CCl4) subcutaneously (twice weekly, 1 ml/kg). These models represent, respectively, a secondary biliary cirrhosis and alcoholic cirrhosis. Mice were killed at several time points to evaluate liver changes by histological and ultrastructural methods. A correlation was made with portal pressure measurements. Histology revealed the absence of fibrosis or cirrhosis in PPVL mice. They developed an isolated portal hypertension. After CBDL induction, the mice developed the characteristics of cirrhosis after 6 weeks, with simultaneous increase in portal pressures. Fifty percent of the mice had ascites at that time point. Sixteen weeks after administration of CCl4, a micronodular cirrhotic aspect of the liver was seen associated with signs of portal hypertension. This is the first descriptive study of three widely used animal models in mice, allowing the study of pathophysiological changes in cirrhosis and portal hypertension. The PPVL in mice leads to a model of isolated portal hypertension. Secondary biliary cirrhosis developed after 6 weeks of common bile duct ligation in 50% of the mice that developed ascites. Subcutaneous injection of CCl4 for 16 weeks induces cirrhosis and poral hypertension, without ascites. Moreover, the present study is the first description of a cirrhotic model in mice developed by subcutaneous injections of CCl4. Well-described mice models will facilitate use of knock-out or transgenic mice and lead to a better understanding of the underlying molecular pathways in the field of portal hypertension and cirrhosis.