金雀异黄酮对慢性阻塞性肺疾病急性加重期模型大鼠肺组织炎症反应的影响  

Effect of genistein on lung inflammation in acute exacerbation of chronic obstructive pulmonary disease model rats

作　　者：张孝侠[1] 吴友涛 ZHANG Xiao-xia;WU You-tao(Medical Laboratory,Jining Medical College,Jining 272067,Shandong Province,China;Department of Emergency,Jining Second People's Hospital,Jining 272049,Shandong Province,China)

机构地区：[1]济宁医学院医学检验实验室,山东济宁272067 [2]济宁市第二人民医院急诊科,山东济宁272049

出　　处：《中国临床药理学杂志》2023年第24期3633-3637,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 观察金雀异黄酮干预对慢性阻塞性肺疾病急性加重期(AECOPD)大鼠炎症反应的抑制作用及其作用机制。方法 采用烟熏结合气道滴注内毒素,并联合鼻腔给菌法构建AECOPD模型,将大鼠随机分为对照组、模型组、地塞米松组和低、高剂量实验组。低、高剂量实验组大鼠分别灌胃给予7、14 mg·kg^(-1)金雀异黄酮,每天1次,直至建模结束;地塞米松组在造模末期灌胃给予1 mg·kg^(-1)地塞米松溶液,每天1次,连续5 d;对照组和模型组大鼠灌胃给予等量的蒸馏水。结束后24 h检测各组大鼠肺功能;以瑞氏-吉姆萨染色检测肺泡灌洗液炎症细胞总数及淋巴细胞、巨噬细胞、中性粒细胞数水平;以试剂盒检测血清中性粒细胞弹性蛋白酶(NE)及炎症因子表达;以实时荧光定量聚合酶链反应(RT-qPCR)法检测黏蛋白5AC(MUC5AC) mRNA表达水平;以蛋白质印迹法检测相关蛋白表达水平。结果 对照组、模型组、低剂量实验组、高剂量实验组、地塞米松组大鼠0.3 s内用力呼气容积/用力肺活量(FEV0.3/FVC)水平分别为(81.57±8.58)%、(53.34±2.75)%、(64.42±6.09)%、(76.24±5.30)%和(79.53±4.73)%;淋巴细胞数分别为(80.19±6.88)×10^(6)、(169.52±57.28)×10^(6)、(130.17±9.01)×10^(6)、(103.55±8.43)×10^(6)和(84.79±7.31)×10^(6)·L^(-1);NE水平分别为(2.02±0.36)、(3.44±0.16)、(3.15±0.24)、(2.34±0.15)和(2.36±0.13) ng·mL^(-1);TNF-α水平分别为(9.43±0.62)、(17.08±1.69)、(14.04±1.47)、(10.18±0.98)和(9.70±0.98) ng·mL^(-1)。模型组上述指标与对照组比较,低剂量实验组、高剂量实验组、地塞米松组上述指标与模型组比较,高剂量实验组上述指标与低剂量实验组比较,差异均有统计学意义(均P<0.05)。结论 金雀异黄酮可抑制炎症因子、NE、MUC5AC表达蛋白,进而改善炎症反应和黏液分泌。Objective To observe the inhibitory effect and mechanism of genistein intervention on inflammation in acute exacerbation of chronic obstructive pulmonary disease(AECOPD) rats.Methods The AECOPD model was established by smoking combined with airway infusion of endotoxin and nasal inoculation.The rats were randomly divided into control group,model group,dexamethasone group and low,high dose experimental groups,with 10 rats in each group.Rats in low,high dose experimental groups were intragaically given 7 mg · kg^(-1) and14 mg·kg^(-1) geni stein,once a day,until the end of modeling.In the dexamethasone group,1 mg·kg^(-1) dexamethasone solution was given intragastatically once a day for 5 days at the end of modeling.Rats in control group and model group were given the same amount of distilled water by intragastric administration.The lung function of each group was detected at 24 h after completion;the total number of inflammatory cells and the number of lymphocytes,macrophages and neutrophils in alveolar lavage fluid were detected by ReichsGiemsa staining;serum neutrophil elastase(NE) and inflammatory factors were detected by the kit;real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was used to detected the levels of Mucin 5 AC(MUC5AC) mRNA;the expression levels of related proteins were detected by Western blot.Results The levels of forced expiratory volume in 0.3 second/forced vital capacity(FEV0.3/FVC) in control group,model group,low dose experimental group,high dose experimental group and dexamethasone group were(81.57 ± 8.58)%,(53.34±2.75) %,(64.42±6.09) %,(76.24±5.30) % and(79.53±4.73) %;the lymphocyte numbers were(80.19±6.88) × 10^(6),(169.52±57.28) × 10^(6),(130.17±9.01) × 10^(6),(103.55±8.43) × 10^(6) and(84.79±7.31) × 10^(6)·L^(-1);NE levels were(2.02±0.36),(3.44±0.16),(3.15±0.24),(2.34±0.15) and(2.36±0.13) ng·mL^(-1);TNF-α levels were(9.43±0.62),(17.08±1.69),(14.04±1.47),(10.18±0.98) and(9.70±0.98) ng·mL^(-1).Compared with control group,the above indexes

关 键 词：金雀异黄酮 慢性阻塞性肺疾病急性加重期 炎症反应 黏液分泌 Toll样受体4/核因子κB通路 

分 类 号：R28[医药卫生—中药学]