硝化应激在纳米氧化镍致大鼠肺组织损伤中的作用  

Role of nitrative stress in nano nickel oxide-induced lung injury in rats

作　　者：刘少堃 朱安[1] 常旭红[1] 孙岩岩[1] 周虹华 孙应彪[1] 邹玲悦 孙铱钒 苏莉[1] 

机构地区：[1]兰州大学公共卫生学院卫生毒理学研究所,兰州730000

出　　处：《卫生研究》2016年第4期563-567,共5页Journal of Hygiene Research

基　　金："本科教学工程"国家级大学生创新创业训练计划项目(No.201510730158);中央高校基本科研业务费专项资金(No.Lzujbky-2015-186)

摘　　要：目的观察纳米氧化镍(NiO)对大鼠的亚慢性肺损伤并从硝化应激角度初步探讨其作用机制。方法 40只健康成年雄性Wistar大鼠随机分为对照组、纳米NiO组(0.015、0.06、0.24 mg/kg)和微米NiO(0.24 mg/kg)组。气管滴注染毒,每周2次,连续6周后HE染色观察肺病理学改变,分光光度法检测肺组织一氧化氮(NO)含量、总一氧化氮合酶(TNOS)和诱导型一氧化氮合酶(iNOS)活性。酶联免疫吸附法检测血清白介素-2(IL-2)、转化生长因子-β(TGF-β)、干扰素-γ(IFN-γ)和8-羟基脱氧鸟苷(8-OHdG)含量。结果组织病理学检查显示,0.06、0.24 mg/kg纳米NiO染毒组出现炎性细胞浸润、肺泡间隔增宽及纳米NiO颗粒聚集等现象。与对照组比较,纳米NiO 0.24 mg/kg组大鼠肺组织匀浆中NO含量、TNOS和iNOS活性均升高(P<0.05)。纳米NiO 0.06和0.24 mg/kg组大鼠血清IL-2、TGF-β和IFN-γ含量升高,纳米NiO 0.24 mg/kg组大鼠血清8-OHd G含量也升高,与对照组比较差异均具有统计学意义(P<0.05)。与微米组比较,纳米NiO 0.24 mg/kg组大鼠肺组织匀浆中NO含量、iNOS活性以及血清IL-2、8-OHdG含量均升高(P<0.05)。结论纳米NiO可引起大鼠肺组织损伤,这可能与其诱导的硝化应激反应有关。Objective To investigate the subchronic lung injury induced by nano nickel oxide（ nano NiO） and its mechanism from the view of nitrative stress in rats.Methods A total of 40 adult male Wistar rats were randomly divided into 5 groups,control group（ normal saline）,0. 015,0. 06 and 0. 24 mg / kg nano NiO groups and 0. 24 mg / kg micro NiO group. Rats received intratracheally instilled nano NiO,micro NiO and normal saline twice a week for 6 weeks,respectively. All rats were sacrificed after the exposure to obtain lung tissues. HE staining was used to observe the lung pathological changes. The content of nitric oxide,and the activities of total nitric oxide synthase（ TNOS） and inducible nitric oxide synthase（ iNOS） in pulmonary tissue homogenate were measured by microplate reader. The levels of interleukin-2（ IL-2）,transforminggrowth factor-beta（ TGF-β）, interferon-gamma（ IFN-γ） and 8-hydroxy-2＇-deoxyguanosine（ 8-OHd G） in serum were detected by enzyme-linked immunosorbent assay（ ELISA）. Results The results of lung histopathology showed that the widened alveolar speta,inflammatory infiltration and nanoparticles deposition increased with the increasing dosage of nano NiO. Compared to control group,the content of NO and the activities of TNOS and iNOS in 0. 24 mg / kg nano NiO group increased in lung homogenate（ P〈0. 05）. The levels of IL-2,TGF-β and IFN-γ in nano NiO 0. 06 and 0. 24 mg /kg group were higher than that of control group,and the level of 8-OHd G increased in nano NiO 0. 24 mg / kg group when compared to control group in serum（ P〈0. 05）. Compared to micro NiO group,the levels of NO and iNOS in lung homogenate,and the serum levels of IL-2 and 8-OHd G increased after exposed to 0. 24 mg / kg nano NiO in rats（ P〈0. 05）.Conclusion Nano NiO can lead to lung injury in rats which may be related with nitrative stress reaction based on pulmonary inflammation.

关 键 词：纳米氧化镍 肺损伤 硝化应激 细胞因子 

分 类 号：R135.2[医药卫生—劳动卫生]