N-乙酰半胱氨酸通过调节NF-κB信号通路减轻纳米氧化铟锡诱导的大鼠肺毒性效应  

N-acetylcysteine regulates NF-κB signaling pathway alleviates the pulmonary toxicity induced by indium-tin oxide nanoparticles in rats

作　　者：李纬康 张意[2] 曲晓雨 林殷乔 赵燕姿 刘楠 Li Weikang;Zhang Yi;Qu Xiaoyu;Lin Yinqiao;Zhao Yanzi;Liu Nan(School of Public Health,North China University of Science and Technology,Hebei Key Laboratory of Occupational Health and Safety for Coal Industry,Tangshan 063210,China;National Institute for Occupational Health and Posion Control,Chinese Center for Disease Control and Prevention,Beijing 100050,China)

机构地区：[1]华北理工大学公共卫生学院,河北省煤矿卫生与安全重点实验室,唐山063210 [2]中国疾病预防控制中心职业卫生与中毒控制所,北京100050

出　　处：《中华劳动卫生职业病杂志》2024年第10期721-729,共9页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：河北省自然科学基金面上项目(H2024209031);唐山市科技计划项目(24130225C)。

摘　　要：目的评估N-乙酰半胱氨酸(NAC)通过调节核因子-κB(NF-κB)信号通路对氧化铟锡纳米颗粒(Nano-ITO)诱导的大鼠肺泡蛋白沉积症(PAP)的可能保护作用。方法于2019年10月,将50只成年雄性SD大鼠随机分为5组(每组10只),分别为空白对照组、生理盐水对照组、NAC对照组(200 mg/kg,腹腔注射)、Nano-ITO组(6 mg/kg Nano-ITO,非暴露式气管灌注)和NAC干预组(大鼠腹腔注射20 mg/kg NAC,1.5 h后气管内灌注6 mg/kg Nano-ITO)。每周染毒2次,共染毒12周。大鼠麻醉下实施处死,取出肺脏进行组织病理学和免疫组化分析。各组间反映氧化应激和肺部炎症的指标比较采用单因素方差分析(ANOVA)和Bonferroni的事后检验进行,并分析NAC对Nano-ITO诱导的大鼠NF-κB信号通路的影响。结果Nano-ITO暴露大鼠的组织病理学检查显示弥漫性肺泡损伤,包括PAP、胆固醇晶体、肺泡纤维化、肺纤维化和肺泡肺气肿。Nano-ITO暴露大鼠的免疫组织化学结果显示,在细支气管和肺泡上皮细胞的细胞核中,核因子κB p65(NF-κB p65)和核因子Kappa B抑制物激酶(IKK-β)呈强阳性,核因子κB抑制蛋白α(IκB-α)呈弱阳性。与空白对照组、生理盐水对照组和NAC对照组比较,Nano-ITO组大鼠支气管肺泡灌洗液中总蛋白(TP)水平明显升高(P<0.05),乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量以及总抗氧化能力(T-AOC)明显增加(P<0.05),促炎细胞因子白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)的水平明显升高(P<0.05),大鼠肺组织中NF-κB p65、IKK-β、诱导型一氧化氮合成酶(iNOS)和活性氧(ROS)水平明显升高(P<0.05)。与Nano-ITO组比较,NAC干预组大鼠支气管肺泡灌洗液中TP水平、T-AOC、MDA含量和TNF-α水平明显降低(P<0.05),大鼠肺组织中NF-κB p65和ROS水平均明显降低(P<0.05)。Western blot结果显示,与各对照组比较,Nano-ITO组大鼠肺组织中NF-κB p65和IKK-β的蛋白表达增ObjectiveThe current study aimed to evaluate the possible protective effects of N-acetylcysteine(NAC)against Indum-tin oxide(ITO)nanoparticle(Nano-ITO)-induced pulmonary alveolar proteinosis(PAP)in rats,especially via modulation of nuclear factor kappa B(NF-κB)signaling.MethodsIn October 2019,50 adult male Sprague-Dawley rats were randomly allocated into five groups(10 rats each)as follows:blank control group,saline control group,NAC control group(200 mg/kg),Nano-ITO group(receiving a repeated intratracheal dose of 6 mg/kg Nano-ITO)and NAC intervention group(pre-treated intraperitoneally with 200 mg/kg NAC 1.5 h before the administration of an intratracheal dose of 6 mg/kg Nano-ITO).The rats were exposed twice a week for 12 weeks.Rats were then euthanized under anesthesia,and their lungs were removed for histopathological and immunohistochemical analysis.The comparison of indicators reflecting oxidative stress and pulmonary inflammation among groups was conducted using one-way analysis of variance(ANOVA)and Bonferroni's test.The effect of NAC on Nano-ITO induced NF-κB signaling pathway in rats was analyzed.ResultsHistopathological examination of Nano-ITO exposed rats revealed diffuse alveolar damage,including PAP,cholesterol crystals,alveolar fibrosis,pulmonary fibrosis,and alveolar emphysema.Immunohistochemical results of Nano-ITO exposed rats showed strong positive for nuclear factorκB p65(NF-κB p65)and nuclear factor Kappa B inhibitory factor kinase(IKK-β)and weak positive for nuclear factorκB inhibitory proteinα(IκB-α)in the nuclei of bronchiolar and alveolar epithelial cells.Compared with blank control group,saline control group and NAC control group,the level of total protein(TP)in bronchoalveolar lavage fluid of rats in Nano-ITO group was significantly increased(P<0.05),and the activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD),malondialdehyde(MDA)content and total antioxidant capacity(T-AOC)were significantly increased(P<0.05),the levels of proinflammatory cytokines interleukin-1�

关 键 词：金属纳米粒子 大鼠 肺泡蛋白沉积症 纳米氧化铟锡 N-乙酰半胱氨酸 NF-ΚB信号通路 

分 类 号：R114[医药卫生—卫生毒理学]