中国药房2025,Vol.36Issue(18):2250-2255,6.DOI:10.6039/j.issn.1001-0408.2025.18.06
白花丹素对AECOPD大鼠炎症反应及氧化应激的影响及机制
Effects and mechanism of plumbagin on the inflammatory response and oxidative stress in rats with AECOPD
摘要
Abstract
OBJECTIVE To explore the effects and potential mechanism of plumbagin on the inflammatory response and oxidative stress in rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)based on Notch1/GATA3 signaling pathway.METHODS Ten rats were randomly selected as the control group;another 65 rats were used to establish the AECOPD model by inhaling cigarette smoke,intratracheal administration of endotoxin,and nasal inoculation of bacteria.The 50 successfully modeled rats were randomly divided into the AECOPD group,plumbagin low-dose group(10 mg/kg),plumbagin high-dose group(50 mg/kg),positive control group(dexamethasone 0.09 mg/kg),and high-dose plumbagin+Jagged1(Notch1 activator)group(50 mg/kg+25 mg/kg),with 10 rats in each group.Each group was administrated intragastrically or intraperitoneally with the corresponding drug solution or normal saline,once a day for 28 consecutive days.After the last administration,the lung function indicators(peak expiratory flow,the ratio of forced expiratory volume in 0.3 seconds to forced vital capacity),the number of inflammatory cells(white blood cells,lymphocytes,neutrophils,macrophages)in bronchoalveolar lavage fluid,the levels of inflammatory factors[interleukin-6(IL-6),IL-10,tumor necrosis factor-α(TNF-α)]in lung tissue,and the contents of oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA)]in lung tissue were all determined in each group;the pathological changes of lung tissue and the pathological scores,as well as protein expressions of mucin 5ac(Muc5ac),Notch1 and GATA3 in lung tissue were also detected.RESULTS Compared with the control group,the lung tissue of the AECOPD group rats showed severe damage to the alveolar wall structure,with a large number of inflammatory cells infiltration and accompanied by pathological changes such as thickening of the airway wall;their lung function indicators,IL-10 level,and SOD content were significantly decreased;while the number of various inflammatory cells,IL-6 and TNF-α levels,MDA content,pathological score,as well as protein expressions of Muc5ac,Notch1 and GATA3 were significantly increased or upregulated(P<0.05).Compared with the AECOPD group,the pathological changes in the lung tissue of the rats in each plumbagin dose group were significantly alleviated,and the above quantitative indicators were significantly improved,and the improvement was more obvious in the plumbagin high-dose group(P<0.05).Jagged1 significantly reversed the protective effect of high-dose plumbagin on lung injury and related indicators in AECOPD rats(P<0.05).CONCLUSIONS Plumbagin can inhibit the inflammatory response and oxidative stress in the lungs of AECOPD rats,alleviate lung damage,and improve lung function.The above effects may be related to the inhibition of the Notch1/GATA3 signaling pathway.关键词
白花丹素/慢性阻塞性肺疾病急性加重期/炎症反应/氧化应激/Notch1/GATA3信号通路Key words
plumbagin/acute exacerbation of chronic obstructive pulmonary disease/inflammatory response/oxidative stress/Notch1/GATA3 signaling pathway分类
医药卫生引用本文复制引用
王亚茹,许佩佩,李士荣..白花丹素对AECOPD大鼠炎症反应及氧化应激的影响及机制[J].中国药房,2025,36(18):2250-2255,6.基金项目
国家重点研发计划项目(No.2020YFA0908204) (No.2020YFA0908204)