Qian Jun, Xu Yaqin, Yu Zhiwei
Department of Pediatrics, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
Can Respir J. 2018 May 2;2018:5259240. doi: 10.1155/2018/5259240. eCollection 2018.
While calcitriol can inhibit airway remodeling in asthmatic mice, the mechanism remains unclear. The purpose of this study was to explore the mechanism of action of calcitriol on airway remodeling in asthma and its interaction with budesonide.
A mouse model of asthma was established by allergic sensitization and challenge with ovalbumin. The mice were treated with budesonide, calcitriol, or budesonide plus calcitriol. The expression of airway remodeling-related proteins, transforming growth factor (TGF) signaling pathway-related proteins, the glucocorticoid receptor, and vitamin D receptor (VDR) was determined by immunohistochemical staining and Western blot analysis. Quantitative real-time PCR was used to determine the expression of microRNA-21 (miR-21) in the lung tissue of mice.
Monotherapy with budesonide or calcitriol inhibited the high expression of collagen type I protein and upregulated the low expression of Smad7 in asthmatic mice. There was a synergistic interaction between budesonide and calcitriol in combined treatment. The expression of miR-21 in the combined treatment group was significantly lower than that in the calcitriol treatment group. VDR expression in the combined treatment group was significantly higher than that of the calcitriol treatment group.
Budesonide and calcitriol have a synergistic effect on airway remodeling in asthmatic mice.
虽然骨化三醇可抑制哮喘小鼠的气道重塑，但其机制尚不清楚。本研究旨在探讨骨化三醇对哮喘气道重塑的作用机制及其与布地奈德的相互作用。
通过卵清蛋白致敏和激发建立小鼠哮喘模型。小鼠分别接受布地奈德、骨化三醇或布地奈德加骨化三醇治疗。采用免疫组织化学染色和蛋白质印迹分析测定气道重塑相关蛋白、转化生长因子（TGF）信号通路相关蛋白、糖皮质激素受体和维生素D受体（VDR）的表达。采用定量实时PCR测定小鼠肺组织中微小RNA-21（miR-21）的表达。
布地奈德或骨化三醇单药治疗可抑制哮喘小鼠I型胶原蛋白的高表达，并上调Smad7的低表达。联合治疗中布地奈德与骨化三醇之间存在协同相互作用。联合治疗组miR-21的表达明显低于骨化三醇治疗组。联合治疗组VDR表达明显高于骨化三醇治疗组。
布地奈德和骨化三醇对哮喘小鼠的气道重塑具有协同作用。
