雾化吸入乙酰半胱氨酸对慢性阻塞性肺疾病大鼠模型肺泡巨噬细胞活力的影响  

Effect of aerosolized acetylcysteine on the activity of alveolar macrophages in rat model of chronic obstructive pulmonary disease

作　　者：石永传 周生辉 周敏[2] 沈卫华 SHI Yong-chuan;ZHOU Sheng-hui;ZHOU Min;SHEN Wei-hua(Department of Pharmacy,Jinshan Branch of The Sixth People's Hospital of Shanghai,Shanghai 201599,China;Department of Respiratory Medicine,Jinshan Branch of The Sixth People's Hospital of Shanghai,Shanghai 201599,China)

机构地区：[1]上海市第六人民医院金山分院药剂科,上海201599 [2]上海市第六人民医院金山分院呼吸科,上海201599

出　　处：《中国临床药理学杂志》2023年第19期2794-2797,共4页The Chinese Journal of Clinical Pharmacology

基　　金：上海市第六人民医院医疗集团科学研究课题资助项目(2019-1);上海市金山区第六周期医学重点专科建设基金资助项目(JSZK2019A04)。

摘　　要：目的探讨乙酰半胱氨酸(NAC)雾化吸入剂对慢性阻塞性肺疾病(COPD)模型大鼠肺泡巨噬细胞活力的影响。方法将40只大鼠随机分为低、中、高剂量实验组和模型组、空白组,每组8只。3个实验组和模型组用香烟烟熏+内毒素滴入方法建立COPD大鼠模型。于建模第16天起,低、中、高剂量实验组分别给予NAC吸入剂3、6、9 mL进行雾化吸入,每天2次,每次20 min;模型组和空白组均于同样时间给予等体积0.9%NaCl进行雾化吸入。5组大鼠均给药15 d。第30天处死大鼠,用噻唑蓝比色法检测肺泡巨噬细胞(AM)的细胞活力,用酶联免疫吸附试验方法检测大鼠外周血血清中肿瘤坏死因子-α(TNF-α)、巨噬细胞炎症蛋白-2(MIP-2)、白细胞介素-10(IL-10)和IL-1β的水平。结果中、高剂量实验组和模型组、空白组AM的光密度值分别为0.55±0.04、0.57±0.09、0.42±0.06和0.90±0.04,TNF-α分别为(71.52±15.20)、(70.64±10.54)、(197.67±38.28)和(60.18±10.60)pg·mL^(-1),MIP-2分别为(106.93±24.97)、(101.41±13.51)、(146.72±26.05)和(58.42±10.87)pg·mL^(-1),IL-10分别为(97.33±20.17)、(101.41±13.51)、(71.43±14.15)和(146.14±19.93)pg·mL^(-1),IL-1β分别为(117.84±27.16)、(111.39±3.54)、(143.84±35.03)和(71.83±15.59)pg·mL^(-1)。中、高剂量实验组的上述指标与模型组比较,差异均有统计学意义(P<0.01,P<0.05)。结论NAC吸入剂对COPD大鼠模型AM细胞活力的下降有部分逆转作用,可部分逆转TNF-α、MIP-2及IL-1β水平的上升及IL-10水平的下降,且以中剂量(6 mL)为最适剂量。Objective To investigate the effect of aerosolized acetylcysteine(NAC)on the activity of alveolar macrophages in rat model of chronic obstructive pulmonary disease(COPD).Methods Forty rats were randomly divided into experimental-L,-M,-H groups,model group and blank group.Three experimental groups and model group were used to establish COPD rat models by cigarette smoking and endotoxin instillation.From the 16th day of modeling,the experimental-L,-M,-H groups were given NAC inhalant 3,6 and 9 mL for atomization inhalation,twice a day for 20 min each time.The model and blank group were given 0.9%Na Cl at the same time for atomization inhalation.All 5groups of rats were administered for 15 days.Rats were sacrificed on the30th day,and the cell viability of alveolar macrophages(AM)was detected by methyl thiazolyl tetrazolium colorimetry,while the levels of tumor necrosis factor-α(TNF-α),macrophage inflammatory protein-2(MIP-2),interleukin10(IL-10)and IL-1βin the rat peripheral serum were measured by enzyme linked immunosorbent assay.Results The optical density values of AM in the experimental-M,-H groups,model group and blank group were0.55±0.04,0.57±0.09,0.42±0.06 and 0.90±0.04;TNF-αlevels were(71.52±15.20),(70.64±10.54),(197.67±38.28)and(60.18±10.60)pg·mL^(-1);MIP-2 levels were(106.93±24.97),(101.41±13.51),(146.72±26.05)and(58.42±10.87)pg·mL^(-1);IL-10 levels were(97.33±20.17),(101.41±13.51),(71.43±14.15)and(146.14±19.93)pg·mL^(-1);IL-βlevels were(117.84±27.16),(111.39±3.54),(143.84±35.03)and(71.83±15.59)pg·mL^(-1),respectively.Compared with the model group,the differences of above indexes in the experimental-M,-H groups were statistically significant(P<0.01,P<0.05).Conclusion NAC inhalant can partially reverse the decline of AM cell activity in COPD rats,and can partially reverse the increase of TNF-α,MIP-2 and IL-1βlevels and the decrease of IL-10 levels,and the medium dose(6 mL)is the optimal dose.

关 键 词：乙酰半胱氨酸 雾化吸入 慢性阻塞性肺疾病 肺泡巨噬细胞活力 细胞因子 

分 类 号：R974[医药卫生—药品]