Regulation of NRF2/PINK1 pathway by rutaecarpine on airway epithelial barrier repair in chronic obstructive pulmonary disease rats
10.13699/j.cnki.1001-6821.2025.01.014
- VernacularTitle:吴茱萸次碱调节NRF2/PINK1通路对慢性阻塞性肺疾病大鼠气道上皮屏障修复作用的研究
- Author:
Song ZHANG
1
;
Bo HONG
1
;
Ling CHEN
1
;
Shen-da CHEN
1
Author Information
1. 宁波市中医院 感染(肺病)科,浙江宁波 315000
- Publication Type:Journal Article
- Keywords:
rutaecarpine;
chronic obstructive pulmonary disease;
nuclear factor erythroid 2-related factor 2/PTEN-induced putative kinase 1 pathway;
airway improvement
- From:
The Chinese Journal of Clinical Pharmacology
2025;41(1):65-70
- CountryChina
- Language:Chinese
-
Abstract:
Objective Based on nuclear factor E2 associated factor 2(NRF2)/PTEN induced hypothesized kinase 1(PINK1)pathway,explored the ameliorating effect of rutaecarpine on chronic obstructive pulmonary disease(COPD)rats and its repairing effect on airway epithelial barrier.Methods COPD rat model were established by smoke combined with airway infusion of lipopolysaccharide;and were randomly divided into model group,control group,and experimental-L group,experimental-M group,experimental-H group,10 rats per group.Another 10 normal rats were selected as the normal group.Experimental-L,-M,-H groups were intraperitoneally injected 15,30 and 60 mg·mL-1 rutaecarpine at the dose of 10 mL·kg-1,respectively.The control group was received 4.05 x 10-2 mg·mL-1 prednisone acetate at the dose of 10 mL·kg-1 by gavage.The normal and model groups were given 0.9％NaCl by intraperitoneal injection.Six groups were treated for 28 days with once a day.The first second forced expiratory volume(FEV1)and forced vital capacity(FVC)of rats were measured by minor animal lung function tester.The levels of interleukin(IL)and interferon-γ(INF-γ)in alveolar lavage fluid were determined by enzyme-linked immunosorbent assay method.The expression levels of PINK1 and NRF2 proteins in the lung tissue were determined by Western blot.Results The levels of FEV1 in the experimental-M group,experimental-H group,control group,model group and normal group were(5.17±0.16),(6.36±0.12),(5.06±0.07),(2.24±0.20)and(6.84±0.11)mL;the levels of FVC were(6.71±0.13),(7.56±0.12),(6.81±0.07),(4.46±0.14)and(7.92±0.11)mL;the levels of IL-12 in alveolar lavage fluid were(7.08±0.51),(9.03±0.54),(7.92±0.79),(3.61±1.01)and(10.15±0.82)pg·mL-1;the levels of IL-9 in alveolar lavage fluid were(22.49±2.27),(15.02±1.41),(17.47±1.84),(38.72±1.28)and(11.78±0.94)pg·mL-1;the levels of INF-γ in alveolar lavage fluid were(13.18±0.54),(16.25±0.60),(15.23±0.43),(6.97±0.89)and(17.22±1.15)pg·mL-1;the relative expression levels of PINK1 protein were 1.10±0.06,1.30±0.09,1.18±0.15,0.42±0.03 and 1.61±0.05;the relative expression levels of NRF2 protein were 0.91±0.05,1.46±0.03,1.35±0.07,0.53±0.07 and 1.64±0.11,respectively.The differences of above indexes were statistically significant between the experimental-M group,experimental-H group,control group and the model group(all P＜0.05).Conclusion Rutaecarpine can inhibit inflammation,improve lung function and repair airway epithelial barrier in COPD rats,and its mechanism may be related to regulating NRF2/PINK1 pathway.
