广西医科大学学报2023，Vol.40Issue(12)：1990-1996,7.DOI:10.16190/j.cnki.45-1211/r.2023.12.009
美罗培南调控JAK2-STAT3-RORyt通路对慢性阻塞性肺疾病大鼠气道重塑的影响
Effect of meropenem on airway remodeling in rats with chronic obstructive pulmonary dis-ease by regulating JAK2-STAT3-RORyt pathway
摘要
Abstract
Objective:To investigate the effect of meropenem(MEP)on airway remodeling in rats with chronic obstructive pulmonary disease(COPD)and its regulatory effect on JAK2-STAT3-RORyt signaling pathway.Methods:Forty rats were randomly divided into control group,COPD group,COPD+MEP group and JAK2 in-hibitor group,with 10 rats in each group.Except for the control group,the COPD rat model was reproduced in the other groups.After establishing the model,the COPD+MEP group received an intramuscular injection of 20 mg/kg MEP into the gluteal muscle,while the JAK2 inhibitor group received an intramuscular injection of 8 mg/kg AG490 into the gluteal muscle.The ratio of forced vital capacity(FVC)to forced expiratory volume in 0.3 sec-ond(FEV0.3)in each group was compared.Hematoxylin-eosin(HE)staining was used to observe the pathomor-phological changes of lung tissue.The number of total cells,neutrophils,lymphocytes and macrophages in bron-choalveolar lavage fluid(BALF)was analyzed.The contents of interleukin(IL)-6,IL-8,tumor necrosis factor(TNF)-α and IL-1β in lung tissue were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA and protein expression of transforming growth factor-β1(TGF-β1),collagen Ⅰ,α-smooth muscle actin(α-SMA),JAK2,STAT3 and RORyt was detected by real-time fluorescence quantitative PCR(RT-qPCR)and western blotting,respectively.Results:Compared with the control group,the body weight and FEV0.3/FVC of the COPD group were decreased,the mRNA and protein expression levels of collagenⅠ,α-SMA,TGF-β1,JAK2,STAT3 and RORyt were increased,and the number of total cells,macrophages,neutrophils and lymphocytes in BALF was increased.The contents of IL-8,IL-6,TNF-α and TGF-β1 in lung tissue were increased(all P＜0.05).HE staining showed that the airway mucosal folds were increased and prolonged,a large number of inflammatory cells clustered around the trachea and blood vessels,and the smooth muscle thickened in the COPD group.Compared with the COPD group,the COPD+MEP group and the JAK2 inhibitor group had lower mRNA and protein expression levels of JAK2,STAT3 and RORyt,and a lower number of total cells,macrophages,neutrophils and lymphocytes in BALF.The contents of IL-8,IL-6,TNF-α and TGF-β1 in lung tissue were decreased(all P＜0.01).Conclusion:MEP can al-leviate airway remodeling in COPD rats by inhibiting JAK2-STAT3-RORyt signaling pathway and pulmonary in-flammation.关键词
美罗培南/慢性阻塞性肺疾病/气道重塑/炎症Key words
meropenem/chronic obstructive pulmonary disease/airway remodeling/inflammation分类
医药卫生引用本文复制引用
邵小美,夏明成,尚亚雪..美罗培南调控JAK2-STAT3-RORyt通路对慢性阻塞性肺疾病大鼠气道重塑的影响[J].广西医科大学学报,2023,40(12):1990-1996,7.基金项目
江苏省优势学科建设工程项目(No.YSHL0211-062) （No.YSHL0211-062）
