中国药房2025，Vol.36Issue(8)：939-944,6.DOI:10.6039/j.issn.1001-0408.2025.08.08
布美他尼对慢性阻塞性肺疾病模型大鼠肺损伤的影响及机制
Effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease model rats
摘要
Abstract
OBJECTIVE To investigate the effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease(COPD)model rats.METHODS COPD rat model was induced by lipopolysaccharide,and they were randomly divided into model group(COPD group),bumetanide low-dose and high-dose groups(Bumetanide-L group,Bumetanide-H group),bumetanide high-dose+Yes-associated protein/transcriptional coactivator containing PDZ-binding motif(YAP/TAZ)signaling pathway activator group(Bumetanide-H+PY-60 group),with 12 rats in each group.Another 12 normal rats were selected as normal control group(Control group).Thirty minutes before modeling,bumetanide/normal saline was inhaled or/and PY-60/normal saline was injected into the tail vein.On the next day after the completion of modeling and drug administration,the pulmonary function index of the rats in each group was measured[forced expiratory volume in 0.3 seconds(FEV0.3),forced vital capacity(FVC),peak expiratory flow(PEF),FEV0.3/FVC].The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β in bronchoalveolar lavage fluid(BALF)were determined;the pathological morphology of lung tissue and degree of pulmonary fibrosis were observed.The expression levels of transforming growth factor-β(TGF-β),α-smooth muscle actin(α-SMA)and TAZ protein as well as the phosphorylation of YAP protein in lung tissues were detected.RESULTS Compared with COPD group,the pathological injury of lung tissue in Bumetanide-L and Bumetanide-H groups was alleviated;the exfoliation of lung epithelial cells,tube wall thickening and the degree of pulmonary fibrosis were alleviated;inflammatory cell infiltration was reduced,and blue collagen deposition was reduced;FEV0.3,FVC,FEV0.3/FVC and PEF were significantly increased,while the lung injury score,levels of TNF-α,IL-6,IL-1β,expression levels of TGF-β,α-SMA and TAZ protein and the phosphorylation of YAP protein were significantly decreased(P＜0.05).PY-60 could significantly reverse the improvement effects of bumetanide on above indexes(P＜0.05).CONCLUSIONS Bumetanide can alleviate lung injury,inflammatory response and pulmonary fibrosis in COPD rats,and its mechanism is related to inhibiting YAP/TAZ signaling pathway.关键词
布美他尼/慢性阻塞性肺疾病/YAP/TAZ信号通路/肺损伤/肺纤维化Key words
bumetanide/chronic obstructive pulmonary disease/YAP/TAZ signaling pathway/lung injury/pulmonary fibrosis分类
医药卫生引用本文复制引用
雷宇,陆婧,贺文娟,顾佳颖,周登峰..布美他尼对慢性阻塞性肺疾病模型大鼠肺损伤的影响及机制[J].中国药房,2025,36(8):939-944,6.基金项目
湖北省自然科学基金项目(No.2022CFB951) （No.2022CFB951）
