摘要
背景:N-乙酰半胱氨酸是谷胱甘肽的前体,可以直接清除氧自由基。然而,N-乙酰半胱氨酸是否通过降低氧化应激反应,减轻吸烟导致的肺损伤尚不完全清楚。目的:探讨N-乙酰半胱氨酸对烟熏大鼠肺组织氧化应激的影响,并阐明其可能的作用机制。方法:将30只雄性大鼠随机分为对照组、烟熏组、烟熏+N-乙酰半胱氨酸组。将烟熏组和烟熏+N-乙酰半胱氨酸组大鼠置于被动吸烟动物染毒系统,每次暴露20支香烟的烟雾中,2次/d,1 h/次,持续8周。N-乙酰半胱氨酸组大鼠每天被动烟熏前给予N-乙酰半胱氨酸200 mg/kg灌胃,持续8周。正常对照组大鼠仅单纯放置在染毒系统内,正常饲养8周。实验方案由沈阳医学院实验动物伦理委员会于2018年10月批准,批准号:研伦审第(2018)85号。结果与结论:①病理观察发现烟熏组大鼠肺组织排列紊乱、肺泡间隔增厚、炎症细胞浸润和间质纤维化,而烟熏+N-乙酰半胱氨酸组肺组织出血、间质内炎症细胞数量显著减少、纤维化程度减轻;②与对照组相比,烟熏组大鼠肺组织丙二醛5和肌醇酶α基因表达升高,超氧化物歧化酶1基因表达显著降低,而N-乙酰半胱氨酸可抑制上述变化;③免疫荧光和Western blot结果均发现烟熏+N-乙酰半胱氨酸组大鼠肺组织丙二醛5和肌醇酶α蛋白表达较烟熏组显著降低,超氧化物歧化酶1蛋白表达较烟熏组升高。此外,烟熏+N-乙酰半胱氨酸组核因子E2相关因子和Keap1蛋白表达明显升高,Bach1蛋白表达显著降低;④结果表明,N-乙酰半胱氨酸通过降低氧化应激对烟熏导致的肺损伤发挥保护作用,其作用机制可能通过激活核因子E2相关因子/Keap1信号通路实现。
BACKGROUND:N-Acetyl-L-cysteine is a precursor of glutathione,which can directly scavenge oxygen free radicals.However,it is not entirely clear whether N-acetyl-L-cysteine can alleviate smoking-induced lung injury by reducing oxidative stress.OBJECTIVE:To investigate the effects of N-acetylcysteine on oxidative stress in lung tissue of smoked rats,and to clarify its possible mechanism of action.METHODS:Thirty male rats were randomly divided into control,smoked and smoked+N-acetylcysteine groups.The rats in the smoked and smoked+N-acetylcysteine groups were placed in the passive smoking animal exposure system,with smoking of 20 cigarettes,twice/d,1 hour/times,for 8 consecutive weeks.The rats in the smoked+N-acetylcysteine group were given 200 mg/kg N-acetylcysteine via gavage before passive smoking daily,for 8 consecutive weeks.The control rats were fed normally for 8 consecutive weeks.The study was approved by the Laboratory Animal Ethical Committee of Shenyang Medical College in October 2018,approval No.(2018)85.RESULTS AND CONCLUSION:(1)Pathological observation showed that the pulmonary tissue was disordered,alveolar septal thickening,inflammatory cell infiltration and interstitial fibrosis in the smoking group,while the pulmonary hemorrhage,the number of inflammatory cells and the degree of fibrosis in the smoking+N-acetylcysteine group were significantly reduced.(2)Compared with the control group,the expression levels of malondialdehyde-5 and inositol-alpha genes were significantly increased,and superoxide dismutase-1 gene expression was significantly decreased in the smoked group,while N-acetylcysteine could inhibit the above changes.(3)Immunofluorescence staining and western blot assay results revealed that the expression levels of malondialdehyde-5 and inositol-alpha in lung tissue of rats in the smoked+N-acetylcysteine group was significantly lower than those in the smoked group,and the expression level of superoxide dismutase-1 was significantly higher than that in the smoked group.In addition,the express
作者
李响
王玮
夏书月
何巍
Li Xiang;Wang Wei;Xia Shuyue;He Wei(Intensive Care Unit of Respiratory,Affiliated Central Hospital of Shenyang Medical College,Shenyang 110024,Liaoning Province,China;Intensive Care Unit of Respiratory,the First Hospital of China Medical University,Shenyang 110001,Liaoning Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2020年第2期254-259,共6页
Chinese Journal of Tissue Engineering Research
基金
沈阳医学院科技基金项目(20182032),项目负责人:李响
沈阳市卫生和计划生育委员会委科研课题计划项目(2017年),项目负责人:李响
国家重点研发计划重大慢性非传染性疾病防控研究重点专项(2016YFC1304502),项目负责人:王玮~~
