背景:肺纤维化(PF)是一种慢性,进步,通常是致命的间质性肺病。中药配方及其活性成份在医治PF方面已显示出潜力。三七皂苷(PNS)是从广泛使用的中药三七(Burkill)F.H.Chen,在肺部疾病治疗中表现出治疗效果。
目的:本研究旨在研究PNS对博莱霉素(BLM)诱导的大鼠PF的影响并阐明可能的机制。
方法:通过气管内给予博来霉素(BLM,5mg/kg)。疾病模型诱导后,用PNS(每天50、100或200mg/kg)或吡非尼酮(PFD,每天50mg/kg),持续28天。肺功能,组织病理学变化,胶原蛋白沉积,评估肺组织中的E-和N-钙黏着蛋白水平。使用基于串联质量标签的定量蛋白质组学分析研究了PNS的作用机理。免疫组织化学,酶联免疫吸附测定(ELISA),进行蛋白质印迹分析以验证蛋白质组结果。
结果:PNS治疗改善肺功能,改善了BLM诱导的肺系数增加,减轻肺泡炎症和纤维化的程度,降低了PF大鼠胶原水平的升高。PNS处理还下调N-cadherin的表达,同时上调E-cadherin的表达。蛋白质组学和生物信息学分析显示,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,蛋白质印迹,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型(AT1R)和ACE2-Ang(1-7)之间的平衡发挥其抗纤维化作用。-MasR轴。
结论:PNS通过调节RAS稳态改善BLM诱导的大鼠PF,是一种新的潜在的PF治疗剂。
BACKGROUND: 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.
OBJECTIVE: This study aimed to investigate the effects and elucidate possible potential mechanisms of PNS on bleomycin (BLM)-induced PF in rats.
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.