Department of Respiratory Medicine Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China.
Department of Respiratory Medicine Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China; Chongqing Key Laboratory of Pediatrics, China.
Int Immunopharmacol. 2024 Jan 25;127:111347. doi: 10.1016/j.intimp.2023.111347. Epub 2023 Dec 16.
Panax notoginseng saponin R1(PNS-R1), derived from Panax notoginseng roots, promotes wound repair, whereas glucocorticoids can inhibit the repair of airway epithelial damage in asthma.
This study investigated whether PNS-R1 counteracts the inhibitory effects of glucocorticoids on the repair of airway epithelial damage in asthma.
In vivo, female C57BL/6 mice were sensitized, challenged with house dust mites (HDM), and treated with dexamethasone, PNS-R1, and/or adenovirus GRβ-shRNA. Airway epithelium damage was examined using pathological sections of the trachea and bronchi, markers of airway inflammation, epithelial cells in bronchoalveolar lavage fluid, and expression of the E-cadherin protein. In vitro, we treated 16HBE cells with dexamethasone, PNS-R1, and/or GRβ-siRNA and detected cell proliferation and migration. The expression of GRβ and key components of MKP-1 and Erk1/2 were detected by western blotting.
In vivo, PNS-R1 reduced airway inflammation, hyperresponsiveness, and mucus hypersecretion; the combination of PNS-R1 and dexamethasone promoted airway epithelial integrity and reduced cell detachment. In vitro, PNS-R1 alleviated the inhibition of bronchial epithelial cell growth, migration, and proliferation by dexamethasone; PNS-R1 promoted GRβ expression, inhibited MKP-1 protein expression, and activated MAPK signaling, thereby promoting airway epithelial cell proliferation and repair.
Panax notoginseng saponin R1 alleviated the inhibitory effect of dexamethasone on the repair of airway epithelial damage in asthmatic mice, likely by promoting the proliferation of airway epithelial cells by stimulating GRβ expression and activating the MAPK pathway.
三七总皂苷 R1(PNS-R1)来源于三七根,可促进伤口愈合,而糖皮质激素可抑制哮喘患者气道上皮损伤的修复。
本研究旨在探讨 PNS-R1 是否拮抗糖皮质激素对哮喘气道上皮损伤修复的抑制作用。
体内实验中,雌性 C57BL/6 小鼠致敏后用屋尘螨激发,给予地塞米松、PNS-R1 及/或腺病毒 GRβ-shRNA 处理,通过气管和支气管病理切片、气道炎症标志物、支气管肺泡灌洗液中的上皮细胞以及 E-钙黏蛋白蛋白表达,观察气道上皮损伤情况。体外实验中,用地塞米松、PNS-R1 及/或 GRβ-siRNA 处理 16HBE 细胞,检测细胞增殖和迁移情况。通过 Western blot 检测 GRβ 及 MKP-1 和 Erk1/2 关键成分的表达。
体内实验中,PNS-R1 减轻气道炎症、气道高反应性和黏液高分泌;PNS-R1 与地塞米松联合应用促进气道上皮完整性,减少细胞脱落。体外实验中,PNS-R1 减轻地塞米松对支气管上皮细胞生长、迁移和增殖的抑制作用;PNS-R1 促进 GRβ 表达,抑制 MKP-1 蛋白表达,激活 MAPK 信号通路,从而促进气道上皮细胞增殖和修复。
三七总皂苷 R1 减轻了地塞米松对哮喘小鼠气道上皮损伤修复的抑制作用,可能通过刺激 GRβ 表达和激活 MAPK 通路促进气道上皮细胞增殖。