肺动脉高压动物模型构建方法及新型技术研究进展

doi:10.12300/j.issn.1674-5817.2025.047

实验动物与比较医学 ›› 2026, Vol. 46 ›› Issue (1): 81-93.DOI: 10.12300/j.issn.1674-5817.2025.047

肺动脉高压动物模型构建方法及新型技术研究进展

陈子宜¹^,², 孙红燕²^,³, 康品方²^,³, 武文娟¹()()

^1.蚌埠医科大学检验医学院, 蚌埠 233000
^2.蚌埠医科大学心脑血管病研究中心生理学教研室, 蚌埠 233000
^3.蚌埠医科大学第一附属医院心血管内科, 蚌埠 233000

收稿日期:2025-03-24 修回日期:2025-07-27 出版日期:2026-02-25 发布日期:2026-02-14
通讯作者: 武文娟（1973—），女，硕士，教授，研究方向：分子诊断学。E-mail：0600032@bbmu.edu.cn。ORCID：0009-0000-5196-7949
作者简介:陈子宜（2000—），女，硕士研究生，研究方向：肺动脉高压。E-mail：3211227658@qq.com
基金资助:
安徽省自然科学基金面上项目“红景天苷调控钾通道KCa介导缺氧性肺血管收缩反应机制研究”(2208085MH192);安徽省高校协同创新项目“3D肺血管类器官模型上缺氧性肺动脉高压的发生、调控及干预”(GXXT-2020-019);安徽省高校优秀青年项目“线粒体ALDH2在糖尿病心肌细胞衰老中的作用机制研究”(2022AH030141);蚌埠医科大学研究生科研创新计划“cGAS-STING信号通路调控低氧性肺动脉高压中的TASK-1的机制研究”(Byycx24022);安徽省临床医学研究转化项目“心脏类器官心肌梗死模型构建及SGB-3403抗心肌损伤药效评价和作用机制研究”(202304295107020087)

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

CHEN Ziyi¹^,², SUN Hongyan²^,³, KANG Pinfang²^,³, WU Wenjuan¹()()

^1.School of Laboratory Medicine, Bengbu Medical University, Bengbu 233000, China
^2.Department of Physiology, Research Center for Cardiovascular and Cerebrovascular Diseases, Bengbu Medical University, Bengbu 233000, China
^3.Department of Cardiovascular Medicine, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China

Received:2025-03-24 Revised:2025-07-27 Published:2026-02-25 Online:2026-02-14
Contact: WU Wenjuan (ORCID:0009-0000-5196-7949), E-mail:0600032@bbmu.edu.cn

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。PH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、炎性反应、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，其不同类型均有各自的独特优势与局限性。单剂量注射野百合碱（monocrotaline，MCT）诱导模型是最常用的实验性PH动物模型之一，被广泛应用于PH的机制研究、药物筛选与疗效评价。该模型操作简便、成本较低，可以在短时间内诱导出PH，但其病理生理机制与人类特发性PH存在一定差异。相比之下，Sugen5416联合慢性低氧诱导的PH模型能较好地模拟PH的发生发展过程，该模型通过将动物置于低氧环境中发生肺血管收缩及重塑，但其造模周期较长，且低氧程度对结果影响较大。除以上2种常用的模型构建方法外，还有多种新兴技术应用于PH研究，如基因编辑工程可以精准探究特定基因在PH中的功能；诱导多能干细胞结合3D类器官技术可以依托个体化建模，保留患者遗传信息，从而打造精准临床转化。每种模型或技术都能从不同层面模拟人类PH的病理过程，其研究成果为理解PH疾病本质提供了关键线索，也为新型治疗靶点的研发提供了重要平台。本文对PH研究用多种动物模型及其新兴技术进行综合性描述，深入分析了各模型/技术的特点、应用场景及局限性，以期为研发新治疗策略和药物提供实验技术支持。

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 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

中图分类号:

Q95-33

陈子宜,孙红燕,康品方,等. 肺动脉高压动物模型构建方法及新型技术研究进展[J]. 实验动物与比较医学, 2026, 46(1): 81-93. DOI: 10.12300/j.issn.1674-5817.2025.047.

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.

图/表 3

参考文献 80

[1]	MOCUMBI A, HUMBERT M, SAXENA A, et al. Pulmonary hypertension[J]. Nat Rev Dis Primers, 2024, 10(1):1. DOI:10.1038/s41572-023-00486-7 .
[2]	BOUCHERAT O, AGRAWAL V, LAWRIE A, et al. The latest in animal models of pulmonary hypertension and right ventricular failure[J]. Circ Res, 2022, 130(9):1466-1486. DOI:10.1161/CIRCRESAHA.121.319971 .
[3]	QIU F, MIAO H R, HUI H L, et al. MHCII^hiLYVE1^loCCR2^hi interstitial macrophages promote medial fibrosis in pulmonary arterioles and contribute to pulmonary hypertension[J]. Circ Res, 2025, 137(1):46-66. DOI:10.1161/CIRCRESAHA.125.326173 .
[4]	ZHAO Y T, DING C M, SU H L, et al. Single test-based diagnosis and subtyping of pulmonary hypertension caused by fibrosing mediastinitis using plasma metabolic analysis[J]. Adv Sci, 2025, 12(17):1-9. DOI:10.1002/advs.202416454 .
[5]	RIVERA-LEBRON B N, CRUZ MOREL K J, RISBANO M G. Postural changes from ventilatory gas exchange in pulmonary hypertension: Is it a practical solution to a complex question?[J]. Respirology, 2020, 25(4):354-355. DOI:10.1111/resp.13691 .
[6]	CHANG M C J, GRIEDER F B. The continued importance of animals in biomedical research[J]. Lab Anim, 2024, 53(11):295-297. DOI:10.1038/s41684-024-01458-4 .
[7]	CARMAN B L, PREDESCU D N, MACHADO R, et al. Plexiform arteriopathy in rodent models of pulmonary arterial hypertension[J]. Am J Pathol, 2019, 189(6):1133-1144. DOI:10.1016/j.ajpath.2019.02.005 .
[8]	LUO A, HAO R R, ZHOU X, et al. Transcriptomic profiling highlights cell proliferation in the progression of experimental pulmonary hypertension in rats[J]. Sci Rep, 2024, 14(1):1-11. DOI:10.1038/s41598-024-64251-w .
[9]	SUN X Q, KLOUDA T, BARNASCONI S, et al. Pneumonectomy combined with SU5416 or monocrotaline pyrrole does not cause severe pulmonary hypertension in mice[J]. Am J Physiol Lung Cell Mol Physiol, 2024, 327(2): L250-L257. DOI:10.1152/ajplung.00105.2024 .
[10]	UKITA R, STOKES J W, WU W K, et al. A large animal model for pulmonary hypertension and right ventricular failure: left pulmonary artery ligation and progressive main pulmonary artery banding in sheep[J]. J Vis Exp, 2021(173): 1-23. DOI:10.3791/62694 .
[11]	WU X H, MA J L, DING D, et al. Experimental animal models of pulmonary hypertension: Development and challenges[J]. Animal Model Exp Med, 2022, 5(3):207-216. DOI:10.1002/ame2.12220 .
[12]	ZIMMER A, TEIXEIRA R B, CONSTANTIN R L, et al. The progression of pulmonary arterial hypertension induced by monocrotaline is characterized by lung nitrosative and oxidative stress, and impaired pulmonary artery reactivity[J]. Eur J Pharmacol, 2021, 891:173699. DOI:10.1016/j.ejphar. 2020. 173699 .
[13]	Sun J, Lin J, Yin D, et al. Androgen receptor inhibitor ameliorates pulmonary arterial hypertension by enhancing the apoptosis level through suppressing the Notch3/Hes5 pathway[J]. Front Pharmacol, 2025, 16:1572489. DOI:10.3389/fphar.2025.1572489 .
[14]	MORALES-CANO D, IZQUIERDO-GARCÍA J L, BARREIRA B, et al. Impact of a TAK-1 inhibitor as a single or as an add-on therapy to riociguat on the metabolic reprograming and pulmonary hypertension in the SUGEN5416/hypoxia rat model[J]. Front Pharmacol, 2023, 14:1021535. DOI:10.3389/fphar.2023.1021535 .
[15]	CAI Z Y, LI J, ZHUANG Q, et al. miR-125a-5p ameliorates monocrotaline-induced pulmonary arterial hypertension by targeting the TGF-β1 and IL-6/STAT3 signaling pathways[J]. Exp Mol Med, 2018, 50(4):45. DOI:10.1038/s12276-018-0068-3 .
[16]	俞佳慧, 巩倩, 庄乐南. 肺动脉高压动物模型及其在药物研究中的应用进展[J]. 实验动物与比较医学, 2023, 43(4):381-397. DOI:10.12300/j.issn.1674-5817.2023.048 .
	YU J H, GONG Q, ZHUANG L N. Animal models of pulmonary arterial hypertension and their application in drug research[J]. Lab Anim Comp Med, 2023, 43(4):381-397. DOI:10.12300/j.issn.1674-5817.2023.048 .
[17]	JIANG H X, DING D D, HE Y Z, et al. Xbp1s-Ddit3 promotes MCT-induced pulmonary hypertension[J]. Clin Sci, 2021, 135(21):2467-2481. DOI:10.1042/CS20210612 .
[18]	谢锦程, 肖梦媛, 邓少东, 等. 肺动脉高压实验模型的研究进展[J]. 中国比较医学杂志, 2023, 33(9):79-89. DOI:10.3969/j.issn.1671-7856.2023.09.010 .
	XIE J C, XIAO M Y, DENG S D, et al. Research progress in experimental models of pulmonary arterial hypertension[J]. Chin J Comp Med, 2023, 33(9):79-89. DOI:10.3969/j.issn.1671-7856.2023.09.010 .
[19]	ROGER THOMPSON A A, LAWRIE A. Targeting vascular remodeling to treat pulmonary arterial hypertension[J]. Trends Mol Med, 2017, 23(1):31-45. DOI:10.1016/j.molmed. 2016.11.005 .
[20]	CHEN X J, YU X, LIAN G L, et al. Canagliflozin inhibits PASMCs proliferation via regulating SGLT1/AMPK signaling and attenuates artery remodeling in MCT-induced pulmonary arterial hypertension[J]. Biomed Pharmacother, 2024, 174:116505. DOI:10.1016/j.biopha.2024.116505 .
[21]	FLORES C V, CHAN S Y. Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape[J]. Expert Opin Ther Targets, 2025, 29(6):327-343. DOI:10.1080/14728222.2025.2507034 .
[22]	GAO G F, CHEN A, YAN Y, et al. Role of insulin signaling dysregulation in pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary arterial hypertension[J]. Front Cardiovasc Med, 2025, 12:1543319. DOI:10.3389/fcvm.2025.1543319 .
[23]	HONG J, ARNESON D, UMAR S, et al. Single-cell study of two rat models of pulmonary arterial hypertension reveals connections to human pathobiology and drug repositioning[J]. Am J Respir Crit Care Med, 2021, 203(8):1006-1022. DOI:10.1164/rccm.202006-2169OC .
[24]	CAHYONO A, IRWANTO, RAHMAN M A, et al. Progression of pulmonary arterial hypertension: a study in model[J]. Open Vet J, 2024, 14(12):3498-3504. DOI:10.5455/OVJ.2024.v14.i12.33 .
[25]	WANG F, XIAO W, LI J W, et al. p16^INK4a promoted progress of MCT induced pulmonary hypertension via maintaining redox balance and autophagy pathway[J]. Biochem Biophys Res Commun, 2025, 749:151385. DOI:10.1016/j.bbrc.2025.151385 .
[26]	TATSUOKA Y, HE Z L, LIN H M, et al. The role of right ventricular systolic pressure and ARISCAT score in perioperative pulmonary risk assessment[J]. Braz J Anesthesiol, 2025, 75(2):844597. DOI:10.1016/j.bjane.2025.844597 .
[27]	YI S W, QU T G, WU H L, et al. Knockdown of PLOD2 inhibits pulmonary artery smooth muscle cell glycolysis under chronic intermittent hypoxia via PI3K/AKT signal[J]. Exp Cell Res, 2025, 446(1):114453. DOI:10.1016/j.yexcr.2025.114453 .
[28]	TASCA S, TÜRCK P, DROSDOWSKI D, et al. Melatonin improves adverse vascular remodelling and redox homeostasis in monocrotaline-induced pulmonary arterial hypertension[J]. Arch Physiol Biochem, 2025, 131(3):455-466. DOI:10.1080/13813455.2024.2446822 .
[29]	FU G H, QIU L, WANG J, et al. Genome-wide characterization of circular RNAs in three rat models of pulmonary hypertension reveals distinct pathological patterns[J]. BMC Genomics, 2025, 26(1):127. DOI:10.1186/s12864-025-11239-z .
[30]	ZHENG R X, XU T T, LIN Y, et al. Are endothelial cell proliferation and mesenchymal transition as distinguishing characteristics of 3-week Sugen5416/hypoxia mice model?[J]. Cardiovasc Res, 2023, 119(8): e140-e141. DOI:10.1093/cvr/cvad074 .
[31]	ISHIBASHI T, INAGAKI T, OKAZAWA M, et al. IL-6/gp130 signaling in CD4⁺ T cells drives the pathogenesis of pulmonary hypertension[J]. Proc Natl Acad Sci USA, 2024, 121(16): e2315123121. DOI:10.1073/pnas.2315123121 .
[32]	CHEN C N, HAJJI N, YEH F C, et al. Restoration of Foxp3⁺ regulatory T cells by HDAC-dependent epigenetic modulation plays a pivotal role in resolving pulmonary arterial hypertension pathology[J]. Am J Respir Crit Care Med, 2023, 208(8):879-895. DOI:10.1164/rccm.202301-0181OC .
[33]	李新雨, 任周新, 赵鹏. 基于肺动脉高压的肺血管丛状病变的鼠类模型的研究进展[J]. 中国比较医学杂志, 2025, 35(4):135-149. DOI:10.3969/j.issn.1671-7856.2025.04.013 .
	LI X Y, REN Z X, ZHAO P. Progress in murine models of pulmonary vascular plexiform lesions of pulmonary arterial hypertension[J]. Chin J Comp Med, 2025, 35(4):135-149. DOI:10.3969/j.issn.1671-7856.2025.04.013 .
[34]	DAI J J, CHEN H Y, FANG J D, et al. Vascular remodeling: the multicellular mechanisms of pulmonary hypertension[J]. Int J Mol Sci, 2025, 26(9):4265. DOI:10.3390/ijms26094265 .
[35]	BENZA R L, GRÜNIG E, SANDNER P, et al. The nitric oxide-soluble guanylate cyclase-cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase[J]. Eur Respir Rev, 2024, 33(171):230183. DOI:10.1183/16000617.0183-2023 .
[36]	SUMI M P, TUPTA B, SONG K, et al. Expression of soluble guanylate cyclase (sGC) and its ability to form a functional heterodimer are crucial for reviving the NO-sGC signaling in PAH[J]. Free Radic Biol Med, 2024, 225:846-855. DOI:10.1016/j.freeradbiomed.2024.11.009 .
[37]	BIKOU O, SASSI Y. The sugen/hypoxia rat model for pulmonary hypertension and right heart failure[J]. Methods Mol Biol, 2024, 2803:163-172. DOI:10.1007/978-1-0716-3846-0_12 .
[38]	HALL I F, KISHTA F, XU Y, et al. Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease[J]. Cardiovasc Res, 2024, 120(3):223-236. DOI:10.1093/cvr/cvae021 .
[39]	LIU Y, MA X P, LEI L L, et al. Smooth muscle cell–specific LKB1 protects against sugen 5416/hypoxia-induced pulmonary hypertension through inhibition of BMP4[J]. Am J Respir Cell Mol Biol, 2025, 72(2):169-180. DOI:10.1165/rcmb. 2023-0430oc .
[40]	VISWANATHAN G, KIRSHNER H F, NAZO N, et al. Single-cell analysis reveals distinct immune and smooth muscle cell populations that contribute to chronic thromboembolic pulmonary hypertension[J]. Am J Respir Crit Care Med, 2023, 207(10):1358-1375. DOI:10.1164/rccm.202203-0441OC .
[41]	KARPOV A A, VAULINA D D, SMIRNOV S S, et al. Rodent models of pulmonary embolism and chronic thromboembolic pulmonary hypertension[J]. Heliyon, 2022, 8(3): e09014. DOI:10.1016/j.heliyon.2022.e09014 .
[42]	LIU W J, ZHANG Y M, LU L W, et al. Expression and correlation of hypoxia-inducible factor-1α (HIF-1α) with pulmonary artery remodeling and right ventricular hypertrophy in experimental pulmonary embolism[J]. Med Sci Monit, 2017, 23:2083-2088. DOI:10.12659/msm.900354 .
[43]	NETO-NEVES E M, BROWN M B, ZARETSKAIA M V, et al. Chronic embolic pulmonary hypertension caused by pulmonary embolism and vascular endothelial growth factor inhibition[J]. Am J Pathol, 2017, 187(4):700-712. DOI:10.1016/j.ajpath.2016.12.004 .
[44]	SINGH S, HOUNG A, REED G L. Releasing the brakes on the fibrinolytic system in pulmonary emboli: unique effects of plasminogen activation and α2-antiplasmin inactivation[J]. Circulation, 2017, 135(11):1011-1020. DOI:10.1161/CIRCULATIONAHA.116.024421 .
[45]	CHEN L D, CHEN X, HUANG Y H, et al. Establishment of mouse models for severe pulmonary hypertension through 'double-hit' strategies[J]. Exp Physiol, 2024, 109(12):2026-2030. DOI:10.1113/EP091833 .
[46]	TEERAPUNCHAROEN K, BAG R. Chronic thromboembolic pulmonary hypertension[J]. Lung, 2022, 200(3):283-299. DOI:10.1007/s00408-022-00539-w .
[47]	杨振文, 王宙明, 李晟, 等. 慢性血栓栓塞性肺动脉高压的治疗进展[J]. 中国心血管杂志, 2024, 29(3):278-282. DOI:10.3969/j.issn.1007-5410.2024.03.016 .
	YANG Z W, WANG Z M, LI S, et al. Treatment progress on chronic thromboembolic pulmonary hypertension[J]. Chin J Cardiovasc Med, 2024, 29(3):278-282. DOI:10.3969/j.issn.1007-5410.2024.03.016 .
[48]	AHN C M, HIROMI M. Chronic thromboembolic pulmonary hypertension: endovascular treatment[J]. Korean Circ J, 2019, 49(3):214-222. DOI:10.4070/kcj.2018.0380 .
[49]	MAHMUD E, MADANI M M, KIM N H, et al. Chronic thromboembolic pulmonary hypertension: evolving therapeutic approaches for operable and inoperable disease[J]. J Am Coll Cardiol, 2018, 71(21):2468-2486. DOI:10.1016/j.jacc.2018.04.009 .
[50]	GHOFRANI H A, KIM N H. Medical and interventional therapies for inoperable CTEPH: a necessary combination?[J]. Lancet Respir Med, 2022, 10(10):926-927. DOI:10.1016/S2213-2600(22)00227-2 .
[51]	MANDRAS S A, MEHTA H S, VAIDYA A. Pulmonary hypertension: a brief guide for clinicians[J]. Mayo Clin Proc, 2020, 95(9):1978-1988. DOI:10.1016/j.mayocp.2020.04.039 .
[52]	PRICE L C, MARTINEZ G, BRAME A, et al. Perioperative management of patients with pulmonary hypertension undergoing non-cardiothoracic, non-obstetric surgery: a systematic review and expert consensus statement[J]. Br J Anaesth, 2021, 126(4):774-790. DOI:10.1016/j.bja.2021.01.005 .
[53]	GRADY R M, CANTER M W, WAN F, et al. Pulmonary-to-systemic arterial shunt to treat children with severe pulmonary hypertension[J]. J Am Coll Cardiol, 2021, 78(5):468-477. DOI:10.1016/j.jacc.2021.05.039 .
[54]	MYERS J W, GHANAYEM N S, CAO Y M, et al. Outcomes of systemic to pulmonary artery shunts in patients weighing less than 3 kg: analysis of shunt type, size, and surgical approach[J]. J Thorac Cardiovasc Surg, 2014, 147(2):672-677. DOI:10.1016/j.jtcvs.2013.09.055 .
[55]	MENG L K, YUAN W, CHI H J, et al. Genetic deletion of CMG2 exacerbates systemic-to-pulmonary shunt-induced pulmonary arterial hypertension[J]. FASEB J, 2021, 35(4): e21421. DOI:10.1096/fj.202000299R .
[56]	SENGSIM J, VIJARNSORN C, CHANTHONG P, et al. Survival comparison in adults with congenital systemic to pulmonary shunt and borderline elevated pulmonary vascular resistance versus Eisenmenger syndrome[J]. Sci Rep, 2024, 14:29891. DOI:10.1038/s41598-024-81834-9 .
[57]	SAVALE L, BENAZZO A, CORRIS P, et al. Transplantation, bridging, and support technologies in pulmonary hypertension[J]. Eur Respir J, 2024, 64(4):2401193. DOI:10.1183/13993003.01193-2024 .
[58]	XIONG M, YAO J P, WU Z K, et al. Fibrosis of pulmonary vascular remodeling in carotid artery-jugular vein shunt pulmonary artery hypertension model of rats[J]. Eur J Cardiothorac Surg, 2012, 41(1):162-166. DOI:10.1016/j.ejcts. 2011.04.031 .
[59]	LATUS H, KARANATSIOS G, BASAN U, et al. Clinical and prognostic value of endothelin-1 and big endothelin-1 expression in children with pulmonary hypertension[J]. Heart, 2016, 102(13):1052-1058. DOI:10.1136/heartjnl-2015-308743 .
[60]	LINDER A N, HSIA J, KRISHNAN S V, et al. Management of systemic to pulmonary shunts and elevated pulmonary vascular resistance[J]. ERJ Open Res, 2023, 9(6). DOI:10.1183/23120541.00271-2023 .
[61]	ZHANG J, GU X, CHENG T L, et al. ASH2L deficiency in smooth muscle drives pulmonary vascular remodeling[J]. Circ Res, 2025, 136(7):719-734. DOI:10.1161/CIRCRESAHA.124. 325539 .
[62]	LI M F, CHEN D D, FAN J N, et al. The efficacy, safety and clinical feasibility of a percutaneous atrial septal shunt device for pulmonary arterial hypertension: a single-center cohort study[J]. Respir Res, 2025, 26(1):67. DOI:10.1186/s12931-025-03159-z .
[63]	MITCHELL S, GOMEZ-ROJAS O, MATHAVAN A, et al. Development of new intrapulmonary shunts in pulmonary arterial hypertension patients treated with sotatercept[J]. Am J Respir Crit Care Med, 2025, 211(7):1300-1302. DOI:10.1164/rccm.202501-0056RL .
[64]	UDDIN F, RUDIN C M, SEN T. CRISPR gene therapy: applications, limitations, and implications for the future[J]. Front Oncol, 2020, 10:1387. DOI:10.3389/fonc.2020.01387 .
[65]	SEKAR D, LAKSHMANAN G, M B. Implications of CRISPR/Cas9 system in Hypertension and its related diseases[J]. J Hum Hypertens, 2021, 35(7):642-644. DOI:10.1038/s41371-020-0378-5 .
[66]	BISSERIER M, MATHIYALAGAN P, ZHANG S H, et al. Regulation of the methylation and expression levels of the BMPR2 gene by SIN3a as a novel therapeutic mechanism in pulmonary arterial hypertension[J]. Circulation, 2021, 144(1):52-73. DOI:10.1161/CIRCULATIONAHA.120.047978 .
[67]	WANG L L, MOONEN J R, CAO A Q, et al. Dysregulated smooth muscle cell BMPR2-ARRB2 axis causes pulmonary hypertension[J]. Circ Res, 2023, 132(5):545-564. DOI:10.1161/CIRCRESAHA.121.320541 .
[68]	刘赛利, 艾可龙, 胡长平. 一氧化氮与肺动脉高压及基于一氧化氮信号通路的肺动脉高压治疗药物研究进展[J]. 中国药理学与毒理学杂志, 2023, 37(10):792-797. DOI:10.3867/j.issn.1000-3002.2023.10.009 .
	LIU S L, AI K L, HU C P. Advances in nitric oxide and pulmonary hypertension and therapeutic drugs based on nitric oxide signaling pathway[J]. Chin J Pharmacol Toxicol, 2023, 37(10):792-797. DOI:10.3867/j.issn.1000-3002.2023.10.009 .
[69]	DOGGRELL S A. Is sotatercept, which traps activins and growth differentiation factors, a new dawn in treating pulmonary arterial hypertension (PAH)?[J]. Expert Opin Biol Ther, 2023, 23(7):589-593. DOI:10.1080/14712598.2023.2221784 .
[70]	EDDAHIBI S, MORRELL N, D'ORTHO M P, et al. Pathobiology of pulmonary arterial hypertension[J]. Eur Respir J, 2002, 20(6):1559-1572. DOI:10.1183/09031936.02.00081302 .
[71]	DEVENDRAN A, KAR S, BAILEY R, et al. The role of bone morphogenetic protein receptor type 2 (BMPR2) and the prospects of utilizing induced pluripotent stem cells (iPSCs) in pulmonary arterial hypertension disease modeling[J]. Cells, 2022, 11(23):3823. DOI:10.3390/cells11233823 .
[72]	WANG T, DUAN Y, LIU D, et al. The effect of transglutaminase-2 inhibitor on pulmonary vascular remodeling in rats with pulmonary arterial hypertension[J]. Clin Exp Hypertens, 2022, 44(2):167-174. DOI:10.1080/10641963.2021.2013493 .
[73]	韩新源, 王顺达, 雍志军, 等. 5-羟色胺通过5-羟色胺2A受体对肺动脉成纤维细胞的激活作用[J]. 山西医科大学学报, 2021, 52(12):1558-1562. DOI:10.13753/j.issn.1007-6611.2021.12.008 .
	HAN X Y, WANG S D, YONG Z J, et al. Activation effect of serotonin on pulmonary artery adventitial fibroblasts through 5-HT_2A receptor[J]. J Shanxi Med Univ, 2021, 52(12):1558-1562. DOI:10.13753/j.issn.1007-6611.2021.12.008 .
[74]	FUJIWARA M, YAGI H, MATSUOKA R, et al. Analysis of genetic mutation and modifier genes in pulmonary arterial hypertension[J]. Nihon Rinsho, 2008, 66(11):2071-2075.
[75]	JIAO Y R, WANG W, LEI P C, et al. 5-HTT, BMPR2, EDN1, ENG, KCNA5 gene polymorphisms and susceptibility to pulmonary arterial hypertension: a meta-analysis[J]. Gene, 2019, 680:34-42. DOI:10.1016/j.gene.2018.09.020 .
[76]	ZHOU K J, ZHAO Z, LI S W, et al. A new glioma grading model based on histopathology and bone morphogenetic protein 2 mRNA expression[J]. Sci Rep, 2020, 10:18420. DOI:10.1038/s41598-020-75574-9 .
[77]	LIU C, YUAN B, CHEN H Y, et al. Effects of miR-375-BMPR2 as a key factor downstream of BMP15/GDF9 on the Smad1/5/8 and Smad2/3 signaling pathways[J]. Cell Physiol Biochem, 2018, 46(1):213-225. DOI:10.1159/000488424 .
[78]	POPP S, SCHMITT-BÖHRER A, LANGER S, et al. 5-HTT deficiency in male mice affects healing and behavior after myocardial infarction[J]. J Clin Med, 2021, 10(14):3104. DOI:10.3390/jcm10143104 .
[79]	CHEN Y F, MA P, BO L, et al. Isorhamnetin alleviates symptoms and inhibits oxidative stress levels in rats with pulmonary arterial hypertension[J]. Iran J Basic Med Sci, 2024, 27(12):1616-1623. DOI:10.22038/ijbms.2024.75860.16421 .
[80]	ZHANG J, JIA Z X, PAN H X, et al. From induced pluripotent stem cell (iPSC) to universal immune cells: literature review of advances in a new generation of tumor therapies[J]. Transl Cancer Res, 2025, 14(4):2495-2507. DOI:10.21037/tcr-24-1087 .

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

肺动脉高压动物模型构建方法及新型技术研究进展

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

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 80

相关文章 15

编辑推荐

Metrics

本文评价

[1]	杨琳, 金梦, 吴汗青, 李顺, 周晓辉. 痘苗病毒天坛株感染AG6小鼠脑病模型的建立与初步分析[J]. 实验动物与比较医学, 2026, 46(1): 3-10.
[2]	廖望钥, 雷爽, 李璇, 郭闵, 周若然. 注意缺陷多动障碍动物模型文献分析及效度评价[J]. 实验动物与比较医学, 2026, 46(1): 66-80.
[3]	杨韵蓉, 吴文郁, 谭跃, 严国锋, 李垚, 卢今. 脑卒中动物模型构建与评价方法评述[J]. 实验动物与比较医学, 2026, 46(1): 94-106.
[4]	刘松, 莫倩茹, 王瑾, 崔颖, 田铃. 黑水虻的主要生物学特性及其作为模式生物的开发应用前景[J]. 实验动物与比较医学, 2025, 45(6): 803-809.
[5]	雷林蓓, 万小娟, 谢婧, 刘雨新, 邹节新, 谢宪兵. 无菌蜜蜂在生物医学研究中的应用、优势与挑战[J]. 实验动物与比较医学, 2025, 45(6): 784-793.
[6]	中国研究型医院学会医学动物实验专家委员会, 中国研究型医院学会神经再生与组织器官损伤修复专业委员会, 中国解剖学会工程解剖学分会. 椎间盘退行性病变的临床前研究动物模型选择指南（2025年版）[J]. 实验动物与比较医学, 2025, 45(5): 524-541.
[7]	刘洋, 程来洋, 郭中坤. 中医病症结合的围绝经期综合征动物模型研究进展[J]. 实验动物与比较医学, 2025, 45(5): 586-595.
[8]	王笑铭, 孟晨晨, 范鹿, 李艳阳, 张军平, 吕仕超. 中医证候类动物模型构建方法概述[J]. 实验动物与比较医学, 2025, 45(5): 596-610.
[9]	高超奇, 祝志波, 孙显东. 大鼠血管重构模型的应用进展与分类分析[J]. 实验动物与比较医学, 2025, 45(5): 542-550.
[10]	刘子琪, 李云英, 李钦, 李元涵, 何芳雁, 温伟波. 脾胃虚寒型胃溃疡动物模型研究进展[J]. 实验动物与比较医学, 2025, 45(5): 574-585.
[11]	刘亚益, 贾云凤, 左一鸣, 张军平, 吕仕超. 心气阴两虚证动物模型的构建方法与评价进展[J]. 实验动物与比较医学, 2025, 45(4): 411-421.
[12]	赵鑫, 王晨曦, 石文清, 娄月芬. 斑马鱼在炎症性肠病机制及药物研究中的应用进展[J]. 实验动物与比较医学, 2025, 45(4): 422-431.
[13]	李会萍, 高洪彬, 温金银, 杨锦淳. 疾病动物模型数字化图谱数据库平台的构建与初步应用[J]. 实验动物与比较医学, 2025, 45(3): 300-308.
[14]	谭邓旭, 马一凡, 刘可, 张延英, 师长宏. 重塑细胞间互动：类器官共培养模型赋能疾病机制与治疗探索[J]. 实验动物与比较医学, 2025, 45(3): 309-317.
[15]	潘颐聪, 蒋汶洪, 胡明, 覃晓. 慢性肾脏病大鼠主动脉钙化模型的术式优化及效果评价[J]. 实验动物与比较医学, 2025, 45(3): 279-289.