慢性阻塞性肺疾病(COPD)是一种常见的疾病,其特征是全身性和肺部炎症。三七皂苷R1(NGR1)在多种疾病中具有抗炎作用。我们旨在探讨NGR1在COPD中的作用和机制。
■通过香烟烟雾暴露建立COPD大鼠,脂多糖注射液,冷刺激。分离并鉴定大鼠气道平滑肌细胞(ASMC)。然后,用NGR1(25或50μM)和香烟烟雾提取物(CSE)处理ASMC。此后,活力,扩散,并测量了ASMC的迁移。此外,细胞周期,炎症相关因素,α-SMA,还检测了ASMC的PI3K/AKT通路相关标志物表达。进行了分子对接实验,以探索NGR1与PI3K的相互作用,TGF-β,P65和AKT。此外,740Y-P(PI3K/Akt通路激动剂)用于验证NGR1对COPD的作用机制。
■NGR1抑制增殖和迁移,但导致CSE触发的ASMC细胞周期停滞。此外,NGR1不仅降低了IL-1β,IL-6、IL-8和TNF-α含量,但也降低了CSE刺激的ASMC中的α-SMA表达。此外,NGR1抑制TGF-β1表达,PI3K,CSE刺激的ASMC中p65和AKT磷酸化。分子对接实验显示NGR1对PI3K具有很强的结合能力,TGF-β1、p65和AKT。值得注意的是,740Y-P逆转了NGR1对CSE诱导的ASMC增殖和迁移的影响。
■NGR1可以抑制CSE诱导的ASMC的增殖和迁移,表明NGR1可能是治疗COPD的候选药物。
UNASSIGNED: Chronic obstructive pulmonary disease (COPD) is a common disorder that is characterized by systemic and lung inflammation. Notoginsenoside R1 (NGR1) displays anti-inflammatory properties in numerous diseases. We aimed to explore the function and mechanism of NGR1 in COPD.
UNASSIGNED: COPD rats were established through cigarette smoke exposure, lipopolysaccharide injection, and cold stimulation. Rat airway smooth muscle cells (ASMCs) were separated and identified. Then, ASMCs were treated with NGR1 (25 or 50 μM) and cigarette smoke extract (CSE). Thereafter, the vitality, proliferation, and migration of ASMCs were measured. Additionally, cell cycle, inflammation-related factors, α-SMA, and PI3K/AKT pathway-related marker expressions of the ASMCs were also detected. Molecular docking experiments were conducted to explore the interaction of NGR1 to PI3K, TGF-β, p65, and AKT. Moreover, 740 Y-P (a PI3K/Akt pathway agonist) were used to validate the mechanism of NGR1 on COPD.
UNASSIGNED: NGR1 inhibited the proliferation and migration, but caused cell cycle arrest for CSE-triggered ASMCs. Furthermore, NGR1 not only decreased IL-1β, IL-6, IL-8, and TNF-α contents, but also reduced α-SMA expression in CSE-stimulated ASMCs. Moreover, NGR1restrainedTGF-β1 expression, PI3K, p65, and AKT phosphorylation in CSE-stimulated ASMCs. Molecular docking experiments showed NGR1 exhibited a strong binding ability to PI3K, TGF-β1, p65, and AKT. Notably, the effects of NGR1 on the proliferation and migration of CSE-induced ASMCs were reversed by 740 Y-P.
UNASSIGNED: NGR1 can restrain the proliferation and migration of CSE-induced ASMCs, indicating that NGR1 may be a therapeutic candidate for treating COPD.