中国临床药理学杂志2026，Vol.42Issue(5)：657-663,7.DOI:10.13699/j.cnki.1001-6821.2026.05.011
雷公藤红素调控Notch途径对慢阻肺大鼠肺成纤维细胞气道影响的研究
Research on the effects of celastrol regulating the Notch pathway on the airway of lung fibroblasts in rats with chronic obstructive pulmonary disease
摘要
Abstract
Objective To investigate the effects of celastrol(Cel)on airway remodeling factors,collagen synthesis and degradation in lung fibroblasts of chronic obstructive pulmonary disease(COPD)rats by regulating the neurogenic locus notch homolog protein(Notch)pathway.Methods A total of 30 rats were randomly divided into 3 groups:animal control group(normal feeding),animal model group(COPD rat model established by smoke exposure combined with lipopolysaccharide tracheal instillation)and animal experimental group(intraperitoneal injection of 0.01 mg·kg-1 Cel after successful modeling).The bronchial fibroblasts(BF)cells were isolated from rats in the animal model group and randomly divided into cell control group(no treatment),cell experimental group(2 μmol·L-1 Cel)and inhibitor group[1 mmol·L-1 valproic acid(VPA)].Pulmonary function was assessed in rats using invasive pulmonary function testing methods;Western blot was used to detect the expression of Notch signaling pathway-related proteins in each group of cells;real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect mRNA expression of airway remodeling-related factors;enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of matrixmetalloproteinase-1(MMP-1)and tissue inhibitors of metalloproteinase-1(TIMP-1)in each group of cells.Results The forced vital capacity(FVC)of rats in animal control group,animal model group and animal experimental group were(6.74±0.87),(3.28±0.51)and(4.94±0.83)mL,respectively;the forced expiratory volume in 0.1 second(FEVO.1)were(3.94±0.45),(1.05±0.16)and(2.41±0.37)mL,respectively;the peak expiratory flow(PEF)were(28.09±4.60),(16.63±3.21)and(21.55±4.02)L·min-1,respectively.Significant differences were observed in the above indicators between animal control group and animal model group,and between animal model group and animal experimental group(P＜0.01,P＜0.001).The relative expression levels of(Notch1)protein in cell control group,cell experimental group and inhibitor group were 1.00±0.19,0.12±0.02 and 0.38±0.06,respectively;the relative expression levels of Notch1 receptor intracellular binding domain(NICD1)protein were 1.00±0.17,0.72±0.12 and 0.85±0.13,respectively;the relative expression levels of serrated typical Notch ligand 1(Jagged 1)protein were 1.00±0.15,0.71±0.11 and 0.84±0.12,respectively;the relative expression levels of hair and enhancer of split 1(Hes1)protein were 1.00±0.11,0.69±0.08 and 0.81±0.09,respectively;the relative expression levels of MMP-9 mRNA were 1.00±0.16,0.59±0.08 and 0.73±0.11,respectively;the relative expression levels of type Ⅰ collagen(Col Ⅰ)mRNA were 1.00±0.14,0.67±0.09 and 0.86±0.14,respectively;the relative expression levels of α-smoth muscle actin(α-SMA)mRNA were 1.00±0.16,0.41±0.07 and 0.78±0.13,respectively;the relative expression levels of transforming growth factor-β(TGF-β)mRNA were 1.00±0.18,0.53±0.09 and 0.75±0.14,respectively;the contents of MMP-1 were(1.19±0.17),(0.80±0.15)and(1.06±0.15)ng·mL-1,respectively;the contents of tissue inhibitor of protease-1(TIMP-1)were(219.78±30.24),(131.94±18.15)and(167.51±21.01)ng·mL-1,respectively.There were all statistically significant differences in the above indicators between cell control group and cell experimental group,as well as between cell experimental group and inhibitor group(P＜0.05,P＜0.01,P＜0.001).Conclusion Celastrol can effectively improve lung function and pulmonary pathological damage in COPD rats,reduce the levels of inflammatory cells and inflammatory factors,and improve the imbalance of airway remodeling-related factors and collagen synthesis/degradation in BF cells,which may be related to its inhibition of Notch signaling activation.关键词
雷公藤红素/慢性阻塞性肺病/神经源性基因Notch同源蛋白途径/气道重塑/成纤维细胞/胶原合成和降解Key words
celastrol/chronic obstructive pulmonary disease/neurogenic locus notch homolog protein pathway/airway remodeling/fibroblast/collagen synthesis and degradation分类
医药卫生引用本文复制引用
李莎莎,邱日皇..雷公藤红素调控Notch途径对慢阻肺大鼠肺成纤维细胞气道影响的研究[J].中国临床药理学杂志,2026,42(5):657-663,7.基金项目
江西省自然科学基金项目面上基金资助项目(20171BAB205004) （20171BAB205004）
赣州市科技计划基金资助项目(2022-YB1282) （2022-YB1282）
