吸入炭黑气溶胶致小鼠肺和外周血的炎性改变及相关性分析

孟涛; 杨墨; 高晔; 叶萌; 段化伟; 戴宇飞; 郑玉新

doi:10.16016/j.1000-5404.201803129

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吸入炭黑气溶胶致小鼠肺和外周血的炎性改变及相关性分析

基础医学 | 更新时间：2026-01-09

- 吸入炭黑气溶胶致小鼠肺和外周血的炎性改变及相关性分析
- Pulmonary and peripheral blood inflammatory responses to black carbon aerosol inhalation in rats and correlation analysis
- 第三军医大学学报 2018年40卷第18期页码：1636-1643
- 作者机构：
  
  1.037009 山西大同，山西大同大学医学院
  2.100050 北京，中国疾病预防控制中心职业卫生与中毒控制所化学污染与健康安全重点实验室
  3.510080 广州，广州市环境污染与健康风险评价重点实验室
  4.266021 山东青岛，青岛大学公共卫生学院
- 作者简介：
  
  [ 郑玉新，E-mail:yx_zheng@139.com ZHENG Yuxin, E-mail:yx_zheng@139.com
- 基金信息：
  
  国家自然科学基金青年科学基金(81502845);国家重点研发计划(2017YFC0211604);广州市环境污染与健康风险评价重点实验室经费资助项目(GZKY2016010)
- DOI：10.16016/j.1000-5404.201803129
  中图分类号： R-332;R135.2;R392.3
- 收稿：2018-03-17，
  
  修回：2018-05-16，
  
  纸质出版：2018-09-30
- 稿件说明：
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孟涛, 杨墨, 高晔, 等. 吸入炭黑气溶胶致小鼠肺和外周血的炎性改变及相关性分析[J]. 第三军医大学学报, 2018,40(18):1636-1643.

Tao MENG, Mo YANG, Ye GAO, et al. Pulmonary and peripheral blood inflammatory responses to black carbon aerosol inhalation in rats and correlation analysis[J]. Journal of Third Military Medical University, 2018, 40(18): 1636-1643.
孟涛, 杨墨, 高晔, 等. 吸入炭黑气溶胶致小鼠肺和外周血的炎性改变及相关性分析[J]. 第三军医大学学报, 2018,40(18):1636-1643. DOI： 10.16016/j.1000-5404.201803129.

Tao MENG, Mo YANG, Ye GAO, et al. Pulmonary and peripheral blood inflammatory responses to black carbon aerosol inhalation in rats and correlation analysis[J]. Journal of Third Military Medical University, 2018, 40(18): 1636-1643. DOI： 10.16016/j.1000-5404.201803129.

摘要

目的

研究反复吸入炭黑气溶胶致小鼠肺和外周血急性期反应蛋白、炎性细胞因子及免疫细胞的改变，并探讨吸入炭黑后肺和外周血炎性改变的相关性。

方法

染毒组将小鼠全身暴露于15.16 mg/m

炭黑气溶胶中6 h/d，分别连续染毒7 d和14 d；恢复组于染毒14 d后恢复14 d，而对照组给予空气。末次染毒24 h或恢复14 d后，收集血液、肺泡灌洗液、肺组织匀浆后进行急性期蛋白、炎性细胞因子及免疫细胞检测。解剖取肺进行病理组织学及超微结构观察。

结果

与对照组相比，染毒7、14 d组肺组织匀浆、肺泡灌洗液及血清中CRP、SAA、IL-6、IL-8、TNF-α水平均显著高于对照组(

0.05)，肺泡灌洗液及外周血中嗜酸性粒细胞百分比显著升高(

0.05)，单核/巨噬细胞百分比显著降低(

0.05)，且这些炎症变化在恢复期并未得到改善。相关分析结果显示，肺组织和外周血的炎性水平存在较好的相关性，且相关系数

=0.665以上。病理检查可见染毒及恢复组肺组织呈灰黑色，镜下支气管壁及肺泡壁结构紊乱、肺间隔增厚、炎性细胞浸润，肺泡腔和肺间隔可见黑色颗粒和巨噬细胞。电镜结果显示，染毒及恢复组巨噬细胞中可见较多溶酶体，且在溶酶体内存在电子密度与炭黑颗粒一致的黑色颗粒。

结论

反复吸入15.16 mg/m

炭黑气溶胶造成小鼠肺组织炭黑颗粒沉积和炎性损伤以及循环系统炎症反应，炭黑吸入后小鼠外周血中炎性生物标志物的变化可以准确地反映肺组织的炎性改变。

Abstract

Objective

To investigate the changes in acute phase reactive proteins

inflammatory cytokines and immune cells in the lungs and peripheral blood in mice exposed to repeated inhalation of black carbon aerosols and explore the correlation of the inhalation and inflammation in the peripheral blood.

Methods

Adult C57BL/6 mice were exposed to black carbon aerosols (15.16 mg/m

) in an inhalation chamber for 6 h per day for 7 or 14 consecutive days

and the mice in the recovery group were exposed for 14 d followed by recovery for another

14 d; the mice in the control group were exposed to filtered air for 6 h per day. At 24 h after the last exposure or after the recovery period

the mice were sacrificed

and the blood samples

bronchoalveolar lavage fluid (BALF) and lung tissues were sampled for analyzing acute phase reactive proteins

inflammatory cytokines and immune cells. The histopathology and ultrastructure of the lung tissue were observed with HE staining and transmission electron microscopy

respectively.

Results

Exposure to black carbon aerosols for 7 and 14 d significantly increased the levels of C-reactive protein (CRP)

amyloid A protein (SAA)

interleukin-6 (IL-6)

IL-8

and tumor necrosis factor-α (TNF-α) in the lung tissue homogenate

BALF and serum (

0.05)

and significantly increased eosinophil percentage (

0.05) and lowered mononuclear cells/macrophage percentage (

0.05) in the BALF and blood. These inflammatory changes were not significantly improved after the recovery period. Correlation analysis showed a strong correlation in the intensity of inflammatory responses between the lungs and the peripheral blood (correlation coefficients all above 0.665). Pathologically

the lung tissue appeared dark gray in the exposure and recovery groups

showing obvious pathologies in the alveoli and bronchioles (disarrangement of bronchial and alveolar walls

thickness of alveolar septum

and infiltration of inflammatory cells) and the presence of black carbon particles and macrophages; transmission electron microscopy revealed numerous lysosomes containing black carbon particles in the alveolar macrophages.

Conclusion

Repeated inhalation of 15.16 mg/m

black carbon aerosols results in carbon particle deposition

inflammatory injury of the lung tissue

and increased levels of systemic inflammatory responses. The changes in peripheral blood inflammatory biomarkers can accurately reflect the inflammatory

levels in the lung tissues after the exposure.

关键词

Keywords

references

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