肺动脉高压动物实验模型的研究进展

doi:10.12300/j.issn.1674-5817.2025-047

摘要/Abstract

摘要：

肺动脉高压（pulmonary hypertension， PH）是一种以肺动脉压力持续升高为特征，致使右心室负荷加重，最终可能引发右心衰竭的疾病。其发病机制涉及多个维度，包括血管内皮功能障碍、血管平滑肌增殖、炎症反应、血栓形成及遗传因素等多个方面。动物模型作为研究PH发病机制和开发治疗策略的核心工具，每种模型都有其独特优势与局限。单剂量注射野百合碱诱导模型，操作简便、成本较低，可以在短时间内诱导出肺动脉高压，但其病理生理机制与人类特发性肺动脉高压存在一定差异。而Sugen5416联合慢性低氧诱导的肺动脉高压模型，能较好地模拟肺动脉高压的发生发展过程，通过将动物置于低氧环境中，引发肺血管收缩及重塑，但造模周期较长，且低氧程度对结果影响较大。除了以上两种常用的构建模型方法，还有多种新兴技术如基因编辑工程，可以精准探究特定基因在肺动脉高压中的功能；诱导多能干细胞结合3D类器官技术，是依托个体化建模保留患者遗传信息打造精准临床转化。每种模型都能从不同层面模拟人类PH的病理过程，为新型治疗靶点的研发提供了重要平台。本文对多种用于构建肺动脉高压的动物模型做了综合性的描述，深入分析了各模型的特点、应用场景及局限性，期望为理解肺动脉高压疾病本质提供关键线索，为研制新治疗策略和药物提供宝贵实验技术支持。

关键词: 肺动脉高压, 动物模型, 野百合碱, Sugen5416, 类器官

Abstract:

Pulmonary hypertension (PH), marked by sustained elevation of pulmonary artery pressure, imposes a heavy burden on the right ventricle and may culminate in right heart failure. Its pathogenesis is multifaceted, encompassing endothelial dysfunction, vascular smooth muscle proliferation, inflammation, thrombosis, and genetic factors. Animal models are indispensable for exploring PH mechanisms and therapies, each with unique strengths and limitations. The single - dose monocrotaline (MCT) model offers simplicity and cost - effectiveness, rapidly inducing PH, yet its pathophysiology differs from human idiopathic PH. In contrast, the Sug en5416 combined with chronic hypoxia model better mimics PH progression by inducing pulmonary vasoconstriction and remodeling under low - oxygen conditions, though it requires a longer modelling time and precise hypoxia control. Beyond these, novel techniques like gene - editing engineering enable precise investigation of specific gene functions in PH. Additionally, induced pluripotent stem cell - based 3D organoid technology allows for individualized modelling while preserving patient genetic information for precise clinical translation. This paper comprehensively describes various PH animal models, analyzing their characteristics, applications, and limitations, to provide crucial insights into PH and support the development of new therapeutic strategies and drugs.

Key words: Pulmonary hypertension, Animal model, Monocrotaline, Sugen5416, Organoid

中图分类号:

Q95-33

陈子宜,孙红燕,康品方,等.肺动脉高压动物实验模型的研究进展[J]. 实验动物与比较医学.. DOI: 10.12300/j.issn.1674-5817.2025-047.

CHEN Ziyi,SUN Hongyan,KANG Pinfang,et al. Research Advances in Animal Experimental Models of Pulmonary Hypertension[J]. Laboratory Animal and Comparative Medicine. DOI: 10.12300/j.issn.1674-5817.2025-047.

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