[1]杜旭升,李东繁△.PM2.5对小鼠肺部自噬、核因子相关因子2、核因子κB表达影响实验研究*[J].陕西医学杂志,2020,49(4):397-400,410.
　DU Xusheng,LI Dongfan..Effects of PM2.5 on lung autophagy and expression of Nrf2 and NF-κB in mice[J].,2020,49(4):397-400,410.
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PM2.5对小鼠肺部自噬、核因子相关因子2、核因子κB表达影响实验研究*
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
49
期数:
2020年4期
页码:
397-400,410
栏目:
基础研究
出版日期:
2020-04-05

文章信息/Info

Title:
Effects of PM2.5 on lung autophagy and expression of Nrf2 and NF-κB in mice
文章编号:
DOI:10.3969/j.issn.10007377.2020.04.003
作者:
杜旭升; 李东繁△
西安交通大学医学院附属西安市中心医院呼吸与危重症医学科(西安710003)
Author(s):
DU Xusheng; LI Dongfan.
Department of Respiratory and Critical Care Medicine,Xi'an Central Hospital,School of Medicine,Xi'an Jiaotong University(Xi'an 710003)
关键词:
PM2.5;  肺部自噬;  核因子相关因子2;  核因子κB;  小鼠;  动物实验
Keywords:
PM2.5;  Pulmonary autophagy;  Nrf2;  NF-κB;  Mice;  Animal experiment
分类号:
R563
文献标志码:
A
摘要:
目的:探究PM2.5对小鼠肺部自噬及核因子相关因子2(Nrf2)、核因子κB(NF-KB)表达的影响。方法:以32只SPF级BALB/c雄性小鼠为研究对象,随机分为正常组、低剂量组、中剂量组和高剂量组。正常组使用生理盐水,低剂量组、中剂量组和高剂量组使用PM2.5,浓度分别为25 mg/L、50 mg/L和100 mg/L,通过雾化进入玻璃容器内。观察不同浓度PM2.5对小鼠肺组织的影响,对不同组别肺部自噬相关蛋白、Nrf2、NF-κB的表达进行检测,将Beas-2B暴露于PM2.5下,激光共聚焦显微镜下对肺部细胞自噬进行观察。结果:随着PM2.5浓度增加,小鼠肺组织结构受损程度、炎性改变均明显增大。与正常组相比,低剂量组、中剂量组和高剂量组LC3Ⅱ/LC3Ⅰ条带分吸光度比值明显较高(P<0.05),且呈现明显的浓度效应关系(P<0.05)。PM2.5暴露可导致小鼠肺部细胞内Nfr2/LaminB、NF-κB p65/LaminB的光密度值明显增加(P<0.05),且具有明显的浓度效应(P<0.05)。对于仅转染pEGFP-LC3质粒的细胞,LC3在胞浆中均一表达,部分细胞细胞核中见少量LC3蛋白聚集,荧光强度较弱。对于转染pEGFP-LC3质粒和PM2.5的细胞,LC3在胞浆中呈现聚集性表达,胞核内现少量明亮荧光斑点,荧光强度明显增强。结论:PM2.5能够使小鼠肺部组织发生炎性改变,且呈浓度依赖性的提高小鼠肺部自噬、Nrf2以及NF-κB水平。
Abstract:
Objective:To study the effects of PM2.5 on lung autophagy and expression of Nrf2 and NF-κB in mice. Method:32 male SPF BALB/c mice were used as the research object and randomly divided into normal group,low-dose group,middle-dose group and high-dose group. Normal group was given normal saline. Low-dose group,medium-dose group and high-dose group were given PM2.5 with concentrations of 25 mg/L,50 mg/L and 100 mg/L,respectively,which were sprayed into glass containers. The effects of different concentrations of PM2.5 on mouse lung tissue were observed. The expression of autophagy-related proteins,Nrf2,NF-κB in different groups of lungs were detected. After exposing Beas-2B to PM2.5,autophagy of lung cells was observed under a laser confocal microscope. Result:With the increase of PM2.5 concentration,the degree of lung tissue damage and inflammatory changes in mice increased significantly. Compared with the normal group,the absorbance ratios of the LC3Ⅱ/LC3Ⅰ bands in others three groups were significantly higher(P<0.05)and showed a significant concentration-effect relationship(P<0.05). PM2.5 exposure significantly increased the optical density of Nfr2/LaminB and NF-κB p65/LaminB in the lung cells of mice(P<0.05),with significant concentration-effect relationship(P<0.05). For cells transfected with the pEGFP-LC3 plasmid only,LC3 was uniformly expressed in the cytoplasm,and a small amount of LC3 protein aggregation was seen in the nucleus of some cells,with weak fluorescence intensity. For the cells transfected with pEGFP-LC3 plasmid and PM2.5,LC3 showed aggregated expression in the cytoplasm,a small number of bright fluorescentspots appeared in the nucleus,and the fluorescence intensity was significantly enhanced. Conclusion:PM2.5 can cause inflammatory changes in the lung tissue of mice,and it can increase the levels of autophagy,Nrf2 and NF-κB in mice in a concentration-dependent manner.

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备注/Memo

备注/Memo:
*陕西省重点研发计划项目(2018SF-267);西安市卫生健康委员会科研项目(J201701002);西安市科技攻关项目[SF-1509(1)]
更新日期/Last Update: 2020-04-13