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  

Regulation of NRF2/PINK1 pathway by rutaecarpine on airway epithelial barrier repair in chronic obstructive pulmonary disease rats

作　　者：张松 洪波 陈玲 陈申达 ZHANG Song;HONG Bo;CHEN Ling;CHEN Shen-da(Department of Infection(Lung Disease),Ningbo Traditional Chinese Medicine Hospital,Ningbo 315000,Zhejiang Province,China)

机构地区：[1]宁波市中医院感染(肺病)科,浙江宁波315000

出　　处：《中国临床药理学杂志》2025年第1期65-70,共6页The Chinese Journal of Clinical Pharmacology

基　　金：浙江省中医药科技计划基金资助项目(2024ZL881,2021ZB257)。

摘　　要：目的基于核因子E2相关因子2(NRF2)/PTEN诱导假定激酶1(PINK1)通路探索吴茱萸次碱对慢性阻塞性肺疾病(COPD)大鼠的改善作用,及其对气道上皮屏障的修复作用。方法用烟熏联合气道滴注脂多糖的方法构建COPD大鼠模型,并随机分为模型组、对照组和低、中、高剂量实验组,每组10只;另取10只正常大鼠作为正常组。低、中、高剂量实验组按10 mL·kg^(-1)的剂量分别腹腔注射15、30、60 mg·mL^(-1)的吴茱萸次碱;对照组按10 mL·kg^(-1)的剂量灌胃给予4.05×10^(-2)mg·mL^(-1)的醋酸泼尼松;正常组和模型组均腹腔注射等量0.9%NaCl。6组大鼠每天给药1次,连续给药28 d。用小动物肺功能测定仪测定大鼠的第1秒用力呼气容积(FEV1)和用力肺活量(FVC),用酶联免疫吸附试验法测定肺泡灌洗液中白细胞介素(IL)和干扰素-γ(INF-γ)的水平,用蛋白质印迹法测定肺组织中PINK1和NRF2蛋白的表达水平。结果中、高剂量实验组和对照组、模型组、正常组的FEV1分别为(5.17±0.16)、(6.36±0.12)、(5.06±0.07)、(2.24±0.20)和(6.84±0.11)mL,FVC分别为(6.71±0.13)、(7.56±0.12)、(6.81±0.07)、(4.46±0.14)和(7.92±0.11)mL,肺泡灌洗液中IL-12水平分别为(7.08±0.51)、(9.03±0.54)、(7.92±0.79)、(3.61±1.01)和(10.15±0.82)pg·mL^(-1),肺泡灌洗液中IL-9水平分别为(22.49±2.27)、(15.02±1.41)、(17.47±1.84)、(38.72±1.28)和(11.78±0.94)pg·mL^(-1),肺泡灌洗液中INF-γ水平分别为(13.18±0.54)、(16.25±0.60)、(15.23±0.43)、(6.97±0.89)和(17.22±1.15)pg·mL^(-1),PINK1蛋白相对表达水平分别为1.10±0.06、1.30±0.09、1.18±0.15、0.42±0.03和1.61±0.05,NRF2蛋白相对表达水平分别为0.91±0.05、1.46±0.03、1.35±0.07、0.53±0.07和1.64±0.11。中、高剂量实验组和对照组的上述指标与模型组相比,在统计学上差异均有统计学意义(均P<0.05)。结论吴茱萸次碱能够抑制COPD大鼠的炎症反应,改善COPD大鼠的肺功能,修复COPD大鼠的气道�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 4.05×10^(-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 we

关 键 词：吴茱萸次碱 慢性阻塞性肺疾病 核因子E2相关因子2/PTEN诱导假定激酶1通路 气道改善 

分 类 号：R28[医药卫生—中药学]