Guan Sibin, Yu Ping, Cao Jianhong, Xi Xiaoling, Zhang Qingliu, Zhu Chenying, Hu Hao, Gong Xin, Fan Huimin
Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine 150 Jimo Road, Shanghai 200120, China.
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine 150 Jimo Road, Shanghai 200120, China.
Am J Transl Res. 2020 Feb 15;12(2):493-506. eCollection 2020.
Chronic obstructive pulmonary disease (COPD) is a devastating and common respiratory disease characterized by chronic inflammation and progressive airway remodeling. Ginsenoside Rg1 (GRg1), a major active component of , has been found to possess beneficial properties against acute lung injury and respiratory diseases. However, the effects of GRg1 on airway remodeling in COPD remain unclear. In this study, we aimed to investigate the potential protective effects of GRg1 on airway remodeling induced by cigarette smoke (CS) and the underlying mechanism. A rat model of COPD was established in which the animals were subjected to CS and GRg1 daily for 12 weeks. Subsequently, we evaluated lung function, inflammatory responses, along with airway remodeling and associated signaling factors. GRg1 treatment was found to improve pulmonary function, reduce airway collagen volume fraction, and markedly reduce the expression of IL-6, TNF-α, α-SMA, and collagen I. Moreover, GRg1 treatment decreased the expression of TGF-β1, TGF-βR1, and phosphorylated-Smad3. , pretreatment of MRC5 human lung fibroblasts with GRg1 prior to exposure to cigarette smoke extract (CSE) reversed the cell ultrastructure disorder, decreased the expression of IL-6 and TNF-α, and significantly attenuated transdifferentiation of MRC5 cells by suppressing α-SMA and collagen I expression. Additionally, GRg1 suppressed the TGF-β1/Smad3 signaling pathway in CSE-stimulated MRC5 cells, whereas Smad3 over-expression abolished the anti-transdifferentiation effect of GRg1. In conclusion, the results of our study demonstrated that GRg1 improves lung function and protects against CS-induced airway remodeling, in part by down-regulating the TGF-β1/Smad3 signaling pathway.
慢性阻塞性肺疾病（COPD）是一种具有破坏性的常见呼吸系统疾病，其特征为慢性炎症和进行性气道重塑。人参皂苷Rg1（GRg1）是[具体物质]的主要活性成分，已被发现具有对抗急性肺损伤和呼吸系统疾病的有益特性。然而，GRg1对COPD气道重塑的影响仍不清楚。在本研究中，我们旨在探讨GRg1对香烟烟雾（CS）诱导的气道重塑的潜在保护作用及其潜在机制。建立了COPD大鼠模型，动物每天接受CS和GRg1处理，持续12周。随后，我们评估了肺功能、炎症反应以及气道重塑和相关信号因子。发现GRg1治疗可改善肺功能，降低气道胶原体积分数，并显著降低IL-6、TNF-α、α-SMA和胶原蛋白I的表达。此外，GRg1治疗降低了TGF-β1、TGF-βR1和磷酸化Smad3的表达。[具体内容]，在暴露于香烟烟雾提取物（CSE）之前用GRg1预处理MRC5人肺成纤维细胞可逆转细胞超微结构紊乱，降低IL-6和TNF-α的表达，并通过抑制α-SMA和胶原蛋白I的表达显著减弱MRC5细胞的转分化。此外，GRg1抑制CSE刺激的MRC5细胞中的TGF-β1/Smad3信号通路，而Smad3过表达消除了GRg1的抗转分化作用。总之，我们的研究结果表明，GRg1可改善肺功能并防止CS诱导的气道重塑，部分原因是通过下调TGF-β1/Smad3信号通路。
