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三七总皂苷调控NF-κB/HIF-1α/VEGF通路干预COPD大鼠肺血管重构的作用机理研究

批准号:
82060815
项目类别:
地区科学基金项目
资助金额:
34.0 万元
负责人:
韩妮萍
依托单位:
学科分类:
中西医结合临床基础
结题年份:
2024
批准年份:
2020
项目状态:
已结题
项目参与者:
韩妮萍

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结项摘要

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中文摘要
慢性阻塞性肺疾病(COPD)是以气道炎症、重塑和肺血管重构为基本病变慢性肺部疾病,已成为全球第三大死因,我国患病人数已超1亿。GOLD以糖皮质激素抗炎和支气管舒张剂解痉为主的治疗方案,能缓解患者症状但不能阻止肺部病变进展和肺功能持续下降的趋势,而辅以中医益气涤痰逐瘀的治法,是减缓病变持续发展的有效策略。课题组前期研究已证实云南省名中医的益肺散结验方及方中的三七能通过抗炎、抗纤维化作用改善COPD病变,但药物对肺血管重构作用尚未深入研究,云南地处高原,改善血瘀状态对缓解患者低氧血症、提高生活质量意义重大。本课题拟以三七有效成分三七总皂苷干预COPD大鼠,观察药物对大鼠肺功能、肺部炎症和肺血管重构病变的改善作用以及其对肺部炎症因子表达和NF-κB/HIF-1α/VEGF通路相关分子的调控规律,揭示PNS干预肺血管重构的可能分子机制,为活血化瘀药物防治COPD提供理论和实验依据。
英文摘要
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by airway inflammation, remodeling and pulmonary vascular remodeling as the basic lesions and continuous airflow limitation. It has become the third leading cause of death worldwide. Over 100 million in our country . GOLD is mainly based on anti-inflammatory glucocorticoids and antispasmodic bronchodilators, which can relieve patients' symptoms but cannot prevent the progress of lung lesions and the continuous decline of lung function. Supplemented by Chinese medicine yiqi ditan zhuyu therapy , is an effective strategy to slow down the continuous development of lesions. The preliminary research of the research group has confirmed that the Huoxue drug Sanqi in the Yifei Sanjie prescription ,which from Yunnan famous TCM doctor,can improve COPD lesions through anti-inflammatory and anti-fibrotic effects, but the effect of intervention on pulmonary vascular remodeling has not been studied in depth. Being on a plateau, improving blood stasis is of great significance to relieve patients with hypoxemia and improve quality of life. Therefore, we will intend to intervene COPD rats with Panax notoginseng, the main active ingredient of Panax notoginseng, to observe the improvement effect of drugs on lung function, pulmonary inflammation and pulmonary vascular remodeling lesions in rats, as well as its expression of inflammatory factors and NF -κB / HIF-1α / VEGF pathway related molecular regulation rules, revealing the possible molecular mechanism of PNS intervention in pulmonary vascular remodeling, providing theoretical and experimental basis for the treatment of COPD with blood circulation and blood stasis drugs.
慢性阻塞性肺疾病(COPD)是以慢性肺部炎症、气道重塑和肺血管重构为基本病变、持续气流受限为基本特征的慢性肺部疾病,临床常以抗炎、解痉为主要治疗方案,因此探究COPD肺血管重构发生机制并筛选有效药物成为研究热点。课题组进行中药及其有效成分干预 COPD 病变的系列研究已经长达二十余年,已证实三七及其有效成分三七总皂苷(PNS)可减轻COPD动物模型气道重塑病变,在此基础上,本课题聚焦COPD肺血管重构病变,探讨PNS是否改善COPD肺血管病变及其机制,明确“益气活血通络”的作用,为从中医药中寻求多靶点防治COPD提供研究基础和有效策略。我们的研究发现:①PNS可改善COPD大鼠症状,升高FEV0.5、FVC、FEV0.5/FVC、MMEF等肺通气功能指标,降低RV、TLC、RV/TLC、FRC等肺容积指标;②PNS可改善COPD大鼠肺部炎症病变,升高肺血管弹力纤维占比降低肺血管胶原占比改善肺血管重构病变;③PNS可降低COPD大鼠血清和肺组织IL-1β、IL-8、TNF-α、ICAM-1、SELE、IL-6、IL-17A、IFN-γ和TGF-β等炎症相关细胞因子和黏附分子浓度和表达;④PNS可负调控TLR4/MyD88/NF-κBp65/HIF-1α/VEGF信号通路蛋白及其mRNA表达;⑤网络药理学分析PNS可能通过调控TLR4/NF-κB通路在COPD疾病中发挥作用;⑥PNS降低LPS/IL-4诱导的巨噬细胞M1/M2炎症相关因子表达,降低M1/M2标志膜分子mRNA表达。. 综上,课题组初步明确:①三七总皂苷可改善COPD大鼠症状和肺功能,减轻其血清和肺组织炎症水平,改善肺部炎症和肺血管重构病变。②三七总皂苷可负调控NF-κB/HIF-1α/VEGF信号通路发挥其疗效,该信号通路可能是COPD肺血管重构的潜在治疗靶点。③三七总皂苷可纠正M1/M2极化失衡,为研究其抗炎、抗纤维化作用提供新的思路。
基于HIF-1α/GLUT-1通路的巨噬细胞代谢重编程探讨三七总皂苷调控COPD小鼠肺部炎症的作用机制研究
  • 批准号:
    82460887
  • 项目类别:
    地区科学基金项目
  • 资助金额:
    32.00万元
  • 批准年份:
    2024
  • 负责人:
    韩妮萍
  • 依托单位:
国内基金
海外基金