三七总皂苷通过调节肾素-血管紧张素系统减轻大鼠肺纤维化。
Panax notoginseng saponin alleviates pulmonary fibrosis in rats by modulating the renin-angiotensin system.
机构信息
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100007, China.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
出版信息
J Ethnopharmacol. 2024 Jan 10;318(Pt B):116979. doi: 10.1016/j.jep.2023.116979. Epub 2023 Jul 31.
ETHNOPHARMACOLOGICAL RELEVANCE
Pulmonary fibrosis (PF) is a chronic, progressive, and often fatal interstitial lung disease. Traditional Chinese medicine formulations and their active ingredients have shown potential in the treatment of PF. Panax notoginseng saponin (PNS) is extracted from the widely used traditional Chinese medicinal herb Panax notoginseng (Burkill) F. H. Chen, exhibiting therapeutic effects in pulmonary diseases treatment.
AIM OF THE STUDY
This study aimed to investigate the effects and elucidate possible potential mechanisms of PNS on bleomycin (BLM)-induced PF in rats.
MATERIALS AND METHODS
PF was induced in rats by intratracheal administration of bleomycin (BLM, 5 mg/kg). After disease model induction, the rats were treated with PNS (50, 100, or 200 mg/kg per day) or pirfenidone (PFD, 50 mg/kg per day) for 28 days. Lung function, histopathological changes, collagen deposition, and E- and N-cadherin levels in lung tissue were evaluated. The mechanism of action of PNS was investigated using tandem mass tag-based quantitative proteomics analysis. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were performed to verify the proteomic results.
RESULTS
PNS treatment improved lung function, ameliorated the BLM-induced increase in the lung coefficient, attenuated the degree of alveolar inflammation and fibrosis, and reduced the elevated collagen level in PF rats. PNS treatment also down-regulated the expression of N-cadherin while up-regulating the expression of E-cadherin. Proteomic and bioinformatic analyses revealed that the renin-angiotensin system (RAS) was closely related to the therapeutic effect of PNS. Immunohistochemistry, Western blot, and ELISA results indicated that PNS exerted its anti-fibrotic effect via regulation of the balance between the angiotensin-converting enzyme (ACE)-angiotensin (Ang)II-AngII receptor type 1 (AT1R) and ACE2-Ang(1-7)-MasR axes.
CONCLUSIONS
PNS ameliorates BLM-induced PF in rats by modulating the RAS homeostasis, and is a new potential therapeutic agent for PF.
民族药理学相关性
肺纤维化（PF）是一种慢性、进行性且常常致命的间质性肺病。中药制剂及其活性成分在 PF 的治疗中显示出潜力。三七总皂苷（PNS）是从广泛使用的中药三七（Burkill）F. H. Chen 中提取的，在肺部疾病治疗中具有治疗作用。
研究目的
本研究旨在探讨 PNS 对博莱霉素（BLM）诱导的大鼠 PF 的作用及其可能的潜在机制。
材料和方法
通过气管内给予博莱霉素（BLM，5mg/kg）诱导 PF 大鼠模型。疾病模型诱导后，大鼠每天给予 PNS（50、100 或 200mg/kg）或吡非尼酮（PFD，50mg/kg）治疗 28 天。评估肺功能、肺组织的组织病理学变化、胶原沉积和 E-和 N-钙黏蛋白水平。使用串联质量标签定量蛋白质组学分析研究 PNS 的作用机制。进行免疫组织化学、酶联免疫吸附测定（ELISA）和 Western blot 分析以验证蛋白质组学结果。
结果
PNS 治疗改善了肺功能，减轻了 BLM 诱导的肺系数增加，减轻了肺泡炎症和纤维化程度，并降低了 PF 大鼠升高的胶原水平。PNS 治疗还下调了 N-钙黏蛋白的表达，同时上调了 E-钙黏蛋白的表达。蛋白质组学和生物信息学分析表明，肾素-血管紧张素系统（RAS）与 PNS 的治疗效果密切相关。免疫组织化学、Western blot 和 ELISA 结果表明，PNS 通过调节血管紧张素转换酶（ACE）-血管紧张素（Ang）II-AngII 受体 1（AT1R）和 ACE2-Ang（1-7）-MasR 轴之间的平衡发挥其抗纤维化作用。
结论
PNS 通过调节 RAS 平衡改善 BLM 诱导的大鼠 PF，是 PF 的一种新的潜在治疗药物。
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