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食管胃静脉曲张动物模型的选择策略与展望
DOI: 10.12449/JCH260527
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：吕天富负责资料分析，图表绘制，初稿撰写；南琼负责研究构思与写作指导；赵颖和王晓华负责文献检索、整理与参考文献校核；穆宁晖和陆炳团负责论文修订，质量把控与终稿审定。
Selection strategies and future perspectives for animal models of gastroesophageal varices
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摘要: 食管胃静脉曲张（GOV）破裂出血作为门静脉高压的严重并发症，病死率高。动物模型是研究其发病机制与治疗策略的重要工具。本文系统综述了各种GOV模型的构建方法，重点探讨各模型在模拟肝静脉压力梯度升高及出血风险等关键病理环节的有效性，并在此基础上提出针对性的模型选择策略。最后，展望了精准医学时代类器官与基因编辑等前沿技术在该领域的应用前景，旨在为GOV的机制探索与临床转化提供模型选择与理论参考。Abstract: Gastroesophageal varices （GOV） bleeding is a severe complication of portal hypertension with a high mortality rate. Animal models are indispensable tools for investigating its pathogenesis and developing novel therapeutic strategies. This article systematically reviews the methods for establishing various GOV models， with a particular focus on their efficacy in simulating the key pathological processes such as an increase in hepatic venous pressure gradient and the risk of bleeding， and it also proposes targeted strategies for model selection. Finally， this article discusses the application prospects of emerging techniques in the era of precision medicine， such as organoids and gene editing， in order to provide model selection and a theoretical reference for exploring the mechanism and clinical translation of GOV.
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Key words:
- Esophageal and Gastric Varices /
- Models， Animal /
- Portal Hypertension
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表 1 GOV动物模型选择策略
Table 1. Strategies for selecting animal models of GOV
研究目的 首选模型 次选模型 选择依据与模型优势 注意事项与局限性 门静脉高压血流动
力学机制研究PVL模型 可充式球囊缩窄法 （1）成模周期短（1～2周），血流动
力学变化显著而稳定；（2）造模成
功率高，动物病死率低；（3）能独
立研究门静脉高压血流动力学，
排除肝硬化复杂背景干扰（1）缺乏肝硬化背景，肝内机制
研究受限；（2）侧支循环解剖结
构存在种属差异；（3）自发性调
节可能导致压力波动肝纤维化/肝硬化机
制及抗纤维化药物
评价CCl4诱导模型 BDL模型 （1）模拟人类肝硬化自然病程；
（2）伴有典型肝功能与组织学异
常；（3）抗纤维化药物疗效评价的
参考依据（1）建模周期长（8～12周）、个体
差异大、病死率高；（2）肝外毒性
干扰药效评估，需长期伦理监督GOV形成机制与一
级预防（药物/内镜）CCl4诱导模型 PVL+CCl4复合模型 （1）模拟GOV渐进性发展；（2）评
估NSBB等对血管重塑的抑制作
用；（3）复合模型可加速进程（1）CCl4模型GOV形成晚（需内
镜/解剖确认）；（2）PVL模型成
模快但结构重塑欠典型急性出血止血材料
与介入器械测试PVL模型 可充式球囊缩窄法 （1）快速建立稳定门静脉高压与
侧支循环，适用于急性实验；（2）
大鼠PVL成本低，适于初筛；（3）
犬、猪模型利于模拟内镜操作（1）自发性出血率极低，常需人
工造瘘模拟；（2）评估止血需注
意种属凝血差异胆汁淤积性门静脉
高压与GOV研究BDL模型 Mdr2基因敲除小鼠 特异性模拟胆汁淤积性肝病的病
理过程，是研究此类疾病相关
GOV的唯一适用模型（1）动物状态差、病死率高；（2）
病理生理改变与常见的病毒肝
炎相关肝硬化/酒精性肝硬化差
异大，结论外推需谨慎门静脉高压病因及
精准医学研究复合模型（如
PVL+CCl4）基因修饰模型
（如TGF-β信号通
路相关基因敲除）（1）模拟多因素复杂病因，贴近于
临床；（2）适用于研究GOV病因异
质性及个体化治疗（1）建模复杂、变量多、成本高；
（2）需高级实验设计和严格对照注：PVL，部分门静脉结扎；CCl4，四氯化碳；BDL，胆总管结扎；GOV，食管胃静脉曲张；NSBB，非选择性β-受体阻滞剂；Mdr2，多药耐药相关蛋白2；TGF-β，转化生长因子β。
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