Research Advances in Construction Methods and Novel Technologies for Animal Models of Pulmonary Hypertension

doi:10.12300/j.issn.1674-5817.2025.047

Abstract

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 serve as core tools for exploring PH mechanisms and therapies, each with unique strengths and limitations. The single-dose monocrotaline (MCT) model is one of the most commonly used experimental animal models of PH and is widely applied in mechanistic studies, drug screening, and efficacy evaluation; it offers simplicity and cost-effectiveness, can induce PH within a short period, yet its pathophysiology differs to some extent from human idiopathic PH. In contrast, the Sugen5416 combined with chronic hypoxia model better mimics PH progression by placing animals under hypoxic conditions to induce pulmonary vasoconstriction and vascular remodeling, but it requires a longer modelling time, and the degree of hypoxia has a substantial impact on experimental outcomes. Beyond these two commonly used modeling approaches, a variety of emerging techniques have been applied in PH research; gene-editing technologies enable precise investigation of specific gene functions in PH. Additionally, induced pluripotent stem cell-based 3D organoid technology allows for individualized modelling while preserving patients' genetic information for precise clinical translation. Each model or technology can simulate different aspects of the pathological processes of human PH, and their findings provide key insights into the nature of the disease and serve as an important platform for the development of novel therapeutic targets. This paper comprehensively describes various animal models and emerging technologies used in PH research, analyzing their characteristics, applications, and limitations, with the aim of providing experimental and technical support for the development of new therapeutic strategies and drugs.

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

CLC Number:

Q95-33

CHEN Ziyi,SUN Hongyan,KANG Pinfang,et al. Research Advances in Construction Methods and Novel Technologies for Animal Models of Pulmonary Hypertension[J]. Laboratory Animal and Comparative Medicine, 2026, 46(1): 81-93. DOI: 10.12300/j.issn.1674-5817.2025.047.

Figures/Tables 3

References 80

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模型类型 Model Type	MCT诱导	SuHx复合	基因编辑	体肺分流术	栓塞性模型	iPSC类器官
机制 Mechanism	内皮损伤、平滑肌增殖、炎症反应	VEGFR2抑制缺氧诱导炎症反应	BMPR2突变、HTT上调、血管重构	血流增加、mPAP升高、右心负荷	血管阻塞、血流动力学改变	细胞分化、类器官形成、基因编辑
最适动物 Optimal Species	大鼠	大鼠	小鼠	幼年羊/猪	大鼠	小鼠
造模方法 Modeling Approach	60~80mg/kg	20mg/kg	位点突变/敲除	导管覆膜支架	血栓栓塞微球颗粒外科手术	重编程技术 3D类器官
病理特征匹配度 Pathological Fidelity	中（血管重构）	高（多机制）	高（位点突变)	中（外科手术）	低（机械阻塞）	超高（个性化）
周期 Timeframe	4周	8周	持续	4~16周	2周	6~8周
死亡率 Mortality Rate	15~20%	30~40%	<5%	15~25%	20~25%	0%
临床相关性 Clinical Relevance	中	高	中	中	低	精准
适应研究场景Applicable Research Context	药物急性筛选	慢性病程机制研究	遗传机制解析	药物筛选和治疗评估	急性栓塞干预机制	个体化治疗策略开发
优缺点 Advantages and Limitations	建模快症状明显操作简单多器官损伤特异性低个体差异大	临床相关性高机制全面表型稳定操作复杂周期较长风险较高	靶向精准稳定可靠机制明确技术复杂环境局限推广受限	改善氧合减轻负荷模拟局限操作复杂风险较高	稳定可靠快速建模创伤较大技术要求高恢复期长	仿生性强个体化准动态模拟成本高昂异质性大功能不全

模型类型 Model Type	MCT诱导	SuHx复合	基因编辑	体肺分流术	栓塞性模型	iPSC类器官
机制 Mechanism	内皮损伤、平滑肌增殖、炎症反应	VEGFR2抑制缺氧诱导炎症反应	BMPR2突变、HTT上调、血管重构	血流增加、mPAP升高、右心负荷	血管阻塞、血流动力学改变	细胞分化、类器官形成、基因编辑
最适动物 Optimal Species	大鼠	大鼠	小鼠	幼年羊/猪	大鼠	小鼠
造模方法 Modeling Approach	60~80mg/kg	20mg/kg	位点突变/敲除	导管覆膜支架	血栓栓塞微球颗粒外科手术	重编程技术 3D类器官
病理特征匹配度 Pathological Fidelity	中（血管重构）	高（多机制）	高（位点突变)	中（外科手术）	低（机械阻塞）	超高（个性化）
周期 Timeframe	4周	8周	持续	4~16周	2周	6~8周
死亡率 Mortality Rate	15~20%	30~40%	<5%	15~25%	20~25%	0%
临床相关性 Clinical Relevance	中	高	中	中	低	精准
适应研究场景Applicable Research Context	药物急性筛选	慢性病程机制研究	遗传机制解析	药物筛选和治疗评估	急性栓塞干预机制	个体化治疗策略开发
优缺点 Advantages and Limitations	建模快症状明显操作简单多器官损伤特异性低个体差异大	临床相关性高机制全面表型稳定操作复杂周期较长风险较高	靶向精准稳定可靠机制明确技术复杂环境局限推广受限	改善氧合减轻负荷模拟局限操作复杂风险较高	稳定可靠快速建模创伤较大技术要求高恢复期长	仿生性强个体化准动态模拟成本高昂异质性大功能不全