N-乙酰半胱氨酸联合阿奇霉素对慢性阻塞性肺疾病模型大鼠氧化应激的影响

 目的:探讨N-乙酰半胱氨酸(NAC)联合阿奇霉素(AZI)对慢性阻塞性肺疾病(COPD) 模型大鼠氧化应激的影响。方法:将60只雄性Wistar大鼠随机分为5组,即正常对照(control)组、模型(model)组、AZI治疗组、NAC治疗组和联合治疗组(AZI+NAC组)。采用烟熏联合气管内滴入脂多糖的方法诱导大鼠COPD模型。NAC组和AZI组大鼠每日烟熏前30 min分别给予NAC和AZI灌胃,AZI+NAC组则给予NAC和AZI联合灌胃。第31天行肺功能检测后处死大鼠,提取支气管肺泡灌洗液(BALF)进行细胞计数,并采用ELISA法测定BALF中白细胞介素-8(IL-8)、白细胞介素-17(IL-17)和肿瘤坏死因子-α(TNF-α)的含量。制作肺组织切片及肺匀浆,测定肺匀浆超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)水平。结果:与control组对比,其余4组均出现肺功能的下降,组织病理提示炎症细胞浸润、肺泡破坏等表现。与control组比较,其余4组BALF中白细胞总数、单核巨噬细胞、中性粒细胞和淋巴细胞均显著增高(P<0.05);与model组、AZI组、NAC组比较,AZI+NAC组BALF中白细胞总数、中性粒细胞和淋巴细胞均显著下降(P<0.05)。与model组对比,AZI组、NAC组和AZI+NAC组IL-8、IL-17、TNF-α和MDA含量均显著降低(P<0.05),SOD和GSH-Px活性均显著增高(P<0.05);与AZI组和NAC组比较,AZI+NAC组IL-8、IL-17、TNF-α和MDA含量均下降,SOD和GSH-Px活性均增高,差异有统计学显著性(P<0.01)。结论:NAC和AZI均能减轻COPD模型大鼠肺部炎症和氧化损伤,两者联合能增强抗氧化作用,可能更适合COPD的临床治疗。

Effects of N-acetylcysteine combined with azithromycin on oxidative stress in rats with chronic obstructive pulmonary disease

AIM: To investigate the effects of N-acetylcysteine (NAC) combined with azithromycin (AZI) on oxidative stress in the rats with chronic obstructive pulmonary disease (COPD). METHODS: Male Wistar rats (n=60) were randomly divided into control group, model group, AZI intervention group,NAC intervention group and AZI+NAC group. The COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide. Each day 30 min prior to smoking, intragastric administration with AZI, NAC or combination of the 2 drugs was given for AZI, NAC, and AZI+NAC groups, respectively. On the 31st day, all rats were killed following lung function test. Cell counts of bronchoalveolar lavage fluid (BALF) were performed, and the contents of interleukin-8 (IL-8), interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) in BALF were measured by ELISA. The histopathology of the lung tissues was observed under light microscope, and the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the lung homogenate were measured. RESULTS: Compared with control group, the other 4 groups showed decreased pulmonary function, and inflammatory cell infiltration and alveolar destruction in histopathology. Compared with control group, the other groups showed higher white blood cells, monocyte-macrophages, neutrophils and lymphocytes in the BALF (P<0.05). Compared with model group, AZI group and NAC group, lower white blood cells, neutrophils and lymphocytes in the BALF were observed in AZI+NAC group (P<0.05). Compared with model group, IL-8, IL-17, TNF-α and MDA in AZI group, NAC group and AZI+NAC group significantly decreased (P<0.05), while SOD and GSH-Px significantly increased (P<0.05). Compared with AZI or NAC group, IL-8, IL-17, TNF-α and MDA in AZI+NAC group significantly decreased (P<0.05), while SOD and GSH-Px increased significantly (P<0.05). CONCLUSION: Both NAC and AZI attenuate the lung inflammation and oxidative damage in COPD model rats. Combined medication exerts preferable anti-oxidation effects, which might be more suitable for the treatment of COPD.