内皮细胞增殖及细胞外基质相关通路调控模型大鼠动脉性肺动脉高压

doi:10.16352/j.issn.1001-6325.2025.06.0770

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (6): 770-776.doi: 10.16352/j.issn.1001-6325.2025.06.0770

内皮细胞增殖及细胞外基质相关通路调控模型大鼠动脉性肺动脉高压

陆晓萱, 郭丽娜, 张红, 宋婉璐, 胡宇飞, 杨沛然^*

中国医学科学院基础医学研究所北京协和医学院基础学院生理学系,北京 100005

收稿日期:2025-03-08 修回日期:2025-04-17 出版日期:2025-06-05 发布日期:2025-05-26
通讯作者: ^*peiran.yang@foxmail.com
基金资助:
四大慢病重大专项(2024ZD0528700);国家自然科学基金(82270062);北京市自然科学基金(7242096)

Endothelial cell proliferation and extracellular matrix-related pathways regulate pulmonary arterial hypertension in rat models

LU Xiaoxuan, GUO Lina, ZHANG Hong, SONG Wanlu, HU Yufei, YANG Peiran^*

Department of Physiology, Institute of Basic Medicine CAMS, School of Basic Medicine PUMC, Beijing 100005, China

Received:2025-03-08 Revised:2025-04-17 Online:2025-06-05 Published:2025-05-26

摘要/Abstract

摘要： 目的应用大鼠模型探究动脉性肺动脉高压(PAH)进展的机制。方法利用皮下注射野百合碱(MCT)及SU5416/低氧的方法构建两种大鼠PAH模型,通过肺组织转录组测序分析PAH大鼠基因表达及通路变化,并与NCBI数据库中的特发性肺动脉高压(IPAH)患者的转录组数据进行交叉比对。结果在两种PAH大鼠模型及IPAH患者肺部,炎性反应相关基因(CXCL9、 CCL24、 SECTM1)表达上调,DGKG、 DOCK9等基因表达下调(P＜0.05);T细胞免疫活化的调控、抗病毒免疫反应相关通路在SU5416/低氧-PAH模型与IPAH患者中均显著上调,细胞外结构及白细胞迁移相关通路在MCT-PAH模型与IPAH患者中均显著上调,而内皮细胞增殖调控通路及细胞外基质(ECM)重塑相关通路在两种模型和IPAH患者中均显著激活(P＜0.05)。结论内皮细胞增殖失衡与ECM重塑异常可能协同驱动PAH的病理进程,对于这些通路的深入研究可为PAH的靶向治疗新药研发提供更多依据。

关键词: 动脉性肺动脉高压(PAH), 动物模型, 内皮细胞, 细胞外基质(ECM)

Abstract: Objective To identify mechanisms regulating disease progression in rat models of pulmonary arterial hypertension (PAH). Methods Rat PAH models were established using subcutaneous monocrotaline (MCT) injection and the SU5416/hypoxia (SU/Hx) method. Transcriptomic sequencing of lung tissues was performed to identify gene expression and pathway alterations in PAH rats, followed by a comparative analysis with transcriptomic data of patients with idiopathic pulmonary arterial hypertension (IPAH) in NCBI database. Results Inflammatory-related genes such as CXCL9, CCL24, and SECTM1 were upregulated in both PAH rat models and IPAH patient lungs, while genes such as DGKG and DOCK9 were downregulated(P＜0.05). Pathways related to endothelial cell proliferation regulation and extracellular matrix (ECM) remodeling were significantly upregulated(P＜0.05). Conclusions The imbalance in endothelial cell proliferation and abnormal ECM remodeling may collectively contribute to PAH pathogenesis. Further exploration of these signaling pathways may provide deep insights for early diagnosis and targeted therapy of PAH.

Key words: pulmonary artery hypertension (PAH), animal model, endothelial cell, extracellular matrix (ECM)

中图分类号:

R543
R331.3

陆晓萱, 郭丽娜, 张红, 宋婉璐, 胡宇飞, 杨沛然. 内皮细胞增殖及细胞外基质相关通路调控模型大鼠动脉性肺动脉高压[J]. 基础医学与临床, 2025, 45(6): 770-776.

LU Xiaoxuan, GUO Lina, ZHANG Hong, SONG Wanlu, HU Yufei, YANG Peiran. Endothelial cell proliferation and extracellular matrix-related pathways regulate pulmonary arterial hypertension in rat models[J]. Basic & Clinical Medicine, 2025, 45(6): 770-776.

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内皮细胞增殖及细胞外基质相关通路调控模型大鼠动脉性肺动脉高压

Endothelial cell proliferation and extracellular matrix-related pathways regulate pulmonary arterial hypertension in rat models

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