紫杉叶素通过调节白细胞趋化性和Ackr受体减轻野百合碱诱导的实验性动脉型肺动脉高压

doi:10.16352/j.issn.1001-6325.2026.08.1082

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (8): 1082-1089.doi: 10.16352/j.issn.1001-6325.2026.08.1082

紫杉叶素通过调节白细胞趋化性和Ackr受体减轻野百合碱诱导的实验性动脉型肺动脉高压

刘祺为^1#, 李霓^2#, 张皓冰¹, 张红¹, 宋婉璐¹, 胡宇飞^1*, 杨沛然^1*

1.中国医学科学院北京协和医学院基础医学研究所呼吸和共病全国重点实验室,北京 100005;
2.中国医学科学院北京协和医学院药物研究所天然药物及核药基础与新药创制全国重点实验室,北京 100050

收稿日期:2026-04-21 修回日期:2026-05-24 发布日期:2026-07-22
通讯作者: ^*peiran.yang@foxmail.com ;hyf20@ibms.pumc.edu.cn
作者简介:^#对本文有相同贡献
基金资助:
中国医学科学院非营利性中央研究院基金(2021-RC310-016)

Taxifolin attenuates monocrotaline-induced experimental pulmonary arterial hypertension by regulating leukocyte chemotaxis and Ackr receptors

LIU Qiwei^1#, LI Ni^2#, ZHANG Haobing¹, ZHANG Hong¹, SONG Wanlu¹, HU Yufei^1*, YANG Peiran^1*

1. State Key Laboratory of Respiratory Health and Comorbidity, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005;
2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Received:2026-04-21 Revised:2026-05-24 Published:2026-07-22
Contact: ^*peiran.yang@foxmail.com ;hyf20@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的探究天然黄酮类化合物紫杉叶素(taxifolin)在实验性动脉型肺动脉高压(PAH)中的治疗作用,并进一步探究其改善PAH的潜在分子机制。方法本研究首先采用网络药理学预测紫杉叶素在PAH中的潜在靶点。用野百合碱(MCT)构建PAH模型后,给大鼠施用紫杉叶素或溶剂,评估血流动力学参数、右心室肥厚和肺血管重构。转录组测序分析潜在的分子机制,并通过免疫荧光染色验证结果。结果网络药理学分析表明,紫杉叶素与白细胞趋化性和血管调节相关的生物学过程密切相关。在MCT诱导的PAH大鼠中,紫杉叶素显著降低了右心室收缩压(P＜0.001),减轻了右心室肥厚(P＜0.05),并抑制了肺小动脉重构(肌化血管数量显著减少:P＜0.000 1,小血管中膜厚度显著降低:P＜0.000 1)。转录组学分析显示,紫杉叶素干预选择性逆转PAH相关趋化因子结合基因的异常表达,并调节Ackr1和Ackr2等非典型趋化因子受体表达,提示其可能通过调控趋化因子信号发挥肺血管保护作用。结论紫杉叶素改善了实验性PAH,在减轻肺血管重构方面显示出疾病修饰作用,其可能通过调节白细胞趋化性实现。这些发现提示了紫杉叶素的治疗潜力,并表明趋化性通路是一个可处理的靶点。

关键词: 动脉型肺动脉高压, 肺血管重塑, 紫杉叶素, 趋化作用, 非典型趋化因子受体

Abstract: Objective To investigate the therapeutic effect of the natural flavonoid taxifolin in experimental pulmonary arterial hypertension (PAH), and to further explore its potential molecular mechanisms underlying the amelioration of PAH. Methods This study first employed network pharmacology to predict the potential targets of taxifolin in PAH. After establishing a PAH model with monocrotaline (MCT), rats were administered with taxifolin or vehicle. Hemodynamic parameters, right ventricular hypertrophy, and pulmonary vascular remodeling were evaluated. Transcriptomic sequencing and analysis were performed to investigate the underlying molecular mechanisms, with results validated through immunofluorescence staining. Results Network pharmacology indicated that taxifolin was closely associated with biological processes related to leukocyte chemotaxis and vascular regulation. In MCT-induced PAH rats, taxifolin significantly reduced right ventricular systolic pressure (P＜0.001), attenuated right ventricular hypertrophy (P＜0.05), and inhibited pulmonary arteriolar remodeling (the number of muscularized vessels was significantly reduced, P＜0.000 1, and the medial wall thickness of small vessels was significantly decreased, P＜0.000 1). Transcriptomic analysis revealed that taxifolin intervention selectively reversed the aberrant expression of PAH-related chemokine-binding genes and regulated the expression of atypical chemokine receptors such as Ackr1 and Ackr2, suggesting that it may exert pulmonary vascular protection through regulating chemokine signaling. Conclusions Taxifolin ameliorates experimental PAH, showing disease-modifying effects in attenuating pulmonary vascular remodeling, potentially through the modulation of leukocyte chemotaxis. These findings suggest the therapeutic potential of taxifolin and highlight the chemotaxis pathway as a tractable target.

Key words: pulmonary arterial hypertension, pulmonary vascular remodeling, taxifolin, chemotaxis, atypical chemokine receptors

中图分类号:

R543.2

刘祺为, 李霓, 张皓冰, 张红, 宋婉璐, 胡宇飞, 杨沛然. 紫杉叶素通过调节白细胞趋化性和Ackr受体减轻野百合碱诱导的实验性动脉型肺动脉高压[J]. 基础医学与临床, 2026, 46(8): 1082-1089.

LIU Qiwei, LI Ni, ZHANG Haobing, ZHANG Hong, SONG Wanlu, HU Yufei, YANG Peiran. Taxifolin attenuates monocrotaline-induced experimental pulmonary arterial hypertension by regulating leukocyte chemotaxis and Ackr receptors[J]. Basic & Clinical Medicine, 2026, 46(8): 1082-1089.

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紫杉叶素通过调节白细胞趋化性和Ackr受体减轻野百合碱诱导的实验性动脉型肺动脉高压

Taxifolin attenuates monocrotaline-induced experimental pulmonary arterial hypertension by regulating leukocyte chemotaxis and Ackr receptors

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