欢迎访问《中国临床药理学与治疗学》杂志官方网站,今天是

中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (1): 61-69.doi: 10.12092/j.issn.1009-2501.2025.01.007

• 基础研究 • 上一篇    下一篇

白花丹素通过调节TGF-β1/Smad2及Nrf2/NOX4通路改善博来霉素诱导的肺纤维化

李慧1,胡恒钊2,俞婷婷1,胡慧娴3,王佳乐4,吴晶4,郝伟1   

  1. 1皖南医学院机能学实验实训中心,芜湖  241002,安徽;2皖南医学院麻醉学院,芜湖  241002,安徽;3皖南医学院医学影像学院,芜湖  241002,安徽;4皖南医学院药学院,芜湖  241002,安徽

  • 收稿日期:2023-10-12 修回日期:2023-11-14 出版日期:2025-01-26 发布日期:2025-01-02
  • 通讯作者: 郝伟,女,硕士,实验师,研究方向:临床药理学。 E-mail: 447385573@qq.com
  • 作者简介:李慧,女,硕士,实验师,研究方向:病理生理学。 E-mail: 11951957@qq.com
  • 基金资助:
    2021年安徽省大学生创新创业训练计划项目(S202110368079);2022年安徽省重点研究与开发计划项目(2022e07020036)

Plumbagin ameliorates pulmonary fibrosis by modulating TGF-β1/Smad2 and Nrf2/NOX4 pathways

LI Hui1, HU Hengzhao2, YU Tingting1, HU Huixian3, WANG Jiale4, WU Jing4, HAO Wei1   

  1. 1 Department of Functional Experimental Training Center, Basic Medical College, Wannan Medical College, Wuhu 241002, Anhui, China; 2 School of Anesthesiology, Wannan Medical College, Wuhu 241002, Anhui, China; 3 School of Medical Imaging, Wannan Medical College, Wuhu 241002, Anhui, China; 4 School of pharmacy, Wannan Medical College, Wuhu 241002, Anhui, China
  • Received:2023-10-12 Revised:2023-11-14 Online:2025-01-26 Published:2025-01-02

摘要:

目的:探究白花丹素(plumbagi,PL)对博来霉素诱导的肺纤维化(pulmonary fibrosis,PF)的保护作用及其可能性机制。方法:将60只雄性C57BL/6小鼠随机分为:对照组(Control)、博来霉素组( bleomycin,BLM)、PL低剂量组(1 mg/kg)、PL高剂量组(2 mg/kg)。采用气管内注射BLM(3 mg/kg)复制小鼠PF模型,腹腔注射PL(1或2 mg/kg)3周,处死动物。HE与Masson染色观察肺组织形态学变化及胶原沉积情况。检测小鼠肺组织中超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)和羟脯氨酸(hydroxyproline,HYP)活性或含量。酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测小鼠肺组织中白介素-6(interleukin-6,IL-6)含量。免疫组化检测小鼠肺组织中核因子相关因子2(nuclear factor related factor 2,Nrf2)和NADPH氧化酶4(reduced nicotinamide adenine dinucleotide phosphate oxidase 4,NOX4)阳性细胞表达。Western blotting检测α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、I型胶原(collagen I,Col I)、III型胶原(collagen III,Col III)、IL-6、转化生长因子-β1(transforming growth factor-β1 ,TGF-β1)、p-Smad2、Nrf2和NOX4的蛋白表达。结果:与BLM组相比,PL治疗可减轻小鼠肺间质损伤及细胞外基质沉积,降低 HYP含量(P<0.01,P<0.05),降低α-SMA、Col I和Col III的蛋白表达(P<0.01,P<0.05),减少IL-6的分泌(P<0.01),提高机体抗氧化能力(增强SOD和GSH的活性,减少MDA含量,P<0.01,P<0.05),显著下调TGF-β1、p-Smad2和NOX4阳性细胞及蛋白表达(P<0.01,P<0.05),上调Nrf2 阳性细胞及蛋白表达(P<0.01,P<0.05)。结论:PL可能通过调节TGF-β1/Smad2及Nrf2/NOX4信号通路减轻炎症反应与胶原沉积,提高机体抗氧化能力,从而延缓PF进程。

关键词: 白花丹素, 肺纤维化, TGF-β1/Smad2信号通路, Nrf2/NOX4信号通路

Abstract:

AIM: To investigate the protective effect of plumbagin (PL) against pulmonary fibrosis (PF) and its possible mechanisms. METHODS: Sixty male C57BL/6 mice were randomly divided into control, bleomycin group (BLM), low dose PL group (1 mg/kg) and high dose PL group (2 mg/kg). The mice PF model was replicated using intratracheal injection of BLM (3 mg/kg),  and then PL (1 or 2 mg/kg) was injected intraperitoneally for 3 weeks and the animals were executed. HE and Masson staining were used to observe morphological changes in lung tissue and collagen deposition. The activities or levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and hydroxyproline (HYP) were measured in mouse lung tissue; ELISA for interleukin-6 (IL-6) in mouse lung tissue. Immunohistochemical detection of nuclear factor-related factor 2 (Nrf2) and reduced nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)  positive cell expression in mouse lung tissue. The expression levels of α-smooth muscle actin (α-SMA), collagen I (Col I), collagen III (Col III), IL-6, transforming growth factor-β1 (TGF-β1), p-Smad2, Nrf2 and NOX4 were detected by Western blotting. RESULTS: Compared with the BLM group, PL treatment attenuated lung parenchymal and interstitial injury and extracellular matrix deposition in mice, reduced HYP content (P<0.01, P<0.05), decreased protein expression of α-SMA, collagen I and III (P<0.01, P<0.05), diminished IL-6 secretion (P<0.01); improved the body's antioxidant capacity (increased SOD and GSH activity and decreased MDA content, P<0.01, P<0.05), significantly down-regulated TGF-β1, p-Smad2 and NOX4-positive cells and protein expression (P<0.01, P<0.05) and up-regulated Nrf2-positive cells and protein expression (P<0.01, P<0.05). CONCLUSION: PL may slow down the PF process by modulating the TGF-β1/Smad2 and Nrf2/NOX4 pathways to attenuate inflammatory responses and collagen deposition and improve the body's antioxidant capacity.

Key words: plumbagin, pulmonary fibrosis, TGF-β1/Smad2 signalling pathway, Nrf2/NOX4 signalling pathway

中图分类号: