乙酰半胱氨酸联合异丙托溴铵对控制大鼠慢性阻塞性肺疾病病程进展的作用  

Effect of N-Acety-L-cysteine combined with ipratropium bromide on progression of chronic obstructive pulmonary disease in rats

作　　者：郭晓雪[1] 马丽伟[2] 李晓宁[2] 刘颖[1] 孙璐瑶[3] 张连莲[4] 于振香[1] 

机构地区：[1]吉林大学第一医院呼吸内科,吉林长春130021 [2]吉林大学白求恩医学院病理生理学系,吉林长春130021 [3]吉林大学第一医院感染症科,吉林长春130021 [4]吉林大学第四医院内科,吉林长春130011

出　　处：《吉林大学学报（医学版）》2013年第4期694-698,I0002,共6页Journal of Jilin University：Medicine Edition

基　　金：吉林省科技厅科研基金资助课题(20110454)

摘　　要：目的:探讨乙酰半胱氨酸(NAC)和异丙托溴氨单独或联合给药对大鼠慢性阻塞性肺疾病(COPD)作用的差异,阐明NAC和异丙托溴氨联合给药的作用机制。方法:选取雄性健康Wistar大鼠30只,随机分为空白对照组、模型组、NAC组、异丙托溴铵组和联合用药组,每组6只。采用3次气管内注入脂多糖及熏香烟3个月的复合刺激法建立COPD大鼠模型,模型建立1周后,于第8天NAC组、异丙托溴铵组和联合用药组大鼠单独或联合给予NAC或异丙托溴铵,持续给药11周。HE染色观察大鼠肺组织形态学变化,血气分析仪检测动脉血血氧指标[二氧化碳分压(PaCO2)和氧分压(PaO2)],ELISA法检测血清白细胞介素6(IL-6)、一氧化氮(NO)及肿瘤坏死因子α(TNF-α)水平。结果:肺组织形态学检测,与模型组比较,各给药组大鼠肺组织气道重塑减轻,以联合用药组减轻最明显。血气分析,与空白对照组比较,模型组大鼠PaO2降低(P<0.01),PaCO2升高(P<0.01);与模型组比较,NAC组、异丙托溴氨组和联合用药组大鼠PaO2明显升高(P<0.05或P<0.01),而PaCO2均明显降低(P<0.05或P<0.01)。ELISA法检测,与空白对照组比较,模型组大鼠血清中IL-6、NO及TNF-α水平升高(P<0.01);与模型组比较,NAC组、异丙托溴氨组和联合用药大鼠IL-6、NO及TNF-α水平均明显降低(P<0.05)。结论:异丙托溴铵和NAC联合应用通过抑制气道重塑可阻止COPD大鼠肺功能进行性下降,控制早期COPD的进展。Objective To study the differences in efficacy of N-Acety-L-cysteine（NAC）and ipratropium bromide alone or co-administered in rats with chronic obstructive pulmonary disease（COPD）,and to clarify the mechanism of co-administration.Methods 30healthy male Wistar rats were randomly divided into blank control group（n=6）,model group（n=6）,NAC group（n=6）,ipratropium bromide group（n=6）and combination of NAC and ipratropium bromide group（n =6）.The rat COPD model was established by intratracheal instillation of lipopolysaccharide（LPS）for 3times and exposing to cigarette smoke for 3months.1week after modeling,on the eighth day the drug NAC or ipratropium bromide were used for 11weeks alone or in combination.HE staining was used to detect the morphological changes of lung tissue;ELISA was used to determine the changes of serum interleukin-6（IL-6）,nitric oxide（NO）,tumor necrosis factor-α（TNF-α）expression;blood-gas analyzer was used to measure the changes of arterial blood oxygen indicators.Results The morphological examination results of lung tissue showed that compared with model group,the lung airway remodeling in drug-treated groups were mitigated,especially in combined treatment group.In expression of inflammatory factors of IL-6,NO,TNF-α,the serum concentration of IL-6,NO,TNF-αof model group was respectively high,compared with blank control group,there is statistical significance（P0.01）.The serum concentration of IL-6,NO,TNF-αof NAC group and ipratropium bromide group was low,compared with model group,there is statistical significance（P0.05）.The results of blood gas analysis showed that the value of PaO2in model group was decreased,compared with blank control group,there was statistical significance（P0.01）;the value of PaO2was increased（P0.01）.Compared with model group,the values of PaO2of the rats in NAC group,ipratropium bromide group and combination group were significantly increased（P0.05or P0.01）,and the values of PaCO2were decreased significantly（

关 键 词：慢性阻塞性肺疾病 肺功能 气道重塑 异丙托溴氨 乙酰半胱氨酸 

分 类 号：R563[医药卫生—呼吸系统]