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
Received:17 March 2018,
Revised:2018-05-16,
Published:30 September 2018
移动端阅览
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.
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.
目的
2
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
2
染毒组将小鼠全身暴露于15.16 mg/m
3
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
2
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(
P
<
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(
P
<
0.05),单核/巨噬细胞百分比显著降低(
P
<
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
r
=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
2
反复吸入15.16 mg/m
3
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。
Objective
2
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
2
Adult C57BL/6 mice were exposed to black carbon aerosols (15.16 mg/m
3
) 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
2
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 (
P
<
0.05)
and significantly increased eosinophil percentage (
P
<
0.05) and lowered mononuclear cells/macrophage percentage (
P
<
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
2
Repeated inhalation of 15.16 mg/m
3
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.
HUSSAIN S, SANGTIAN S, ANDERSON S M, et al . Inflammasome activation in airway epithelial cells after multi-walled carbon nanotube exposure mediates a profibrotic response in lung fibroblasts[J ] . Part Fibre Toxicol, 2014, 11(1): 28. DOI: 10.1186/1743-8977-11-28.
DELFINO R J, SIOUTAS C, MALIK S. Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health[J]. Environ Health Perspect, 2005, 113(8): 934-946. DOI: 10.1289/ehp.7938.
NIWA Y, HIURA Y, SAWAMURA H, et al . Inhalation exposure to carbon black induces inflammatory response in rats[J ] . Circ J, 2008, 72(1): 144-149. DOI: 10.1253/circj.72.144.
VESTERDAL L K, FOLKMANN J K, JACOBSEN N R, et al . Pulmonary exposure to carbon black nanoparticles and vascular effects[J ] . Part Fibre Toxicol, 2010, 7(1): 33. DOI: 10.1186/1743-8977-7-33.
TOTLANDSDAL A I, REFSNES M, LÅG M. Mechanisms involved in ultrafine carbon black-induced release of IL-6 from primary rat epithelial lung cells[J]. Toxicol In Vitro, 2010, 24(1): 10-20. DOI: 10.1016/j.tiv.2009.09.016.
VAL S, HUSSAIN S, BOLAND S, et al . Carbon black and titanium dioxide nanoparticles induce pro-inflammatory responses in bronchial epithelial cells: need for multiparametric evaluation due to adsorption artifacts[J ] . Inhal Toxicol, 2009, 21(Suppl 1): 115-122. DOI: 10.1080/ 0895837 0902942533.
TOTSUKA Y, HIGUCHI T, IMAI T, et al . Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems[J ] . Part Fibre Toxicol, 2009, 6(1): 23. DOI: 10.1186/1743-8977-6-23.
KIM J K, KANG M G, CHO H W, et al . Effect of nano-sized carbon black particles on lung and circulatory system by inhalation exposure in rats[J ] . Saf Health Work, 2011, 2(3): 282-289. DOI: 10.5491/SHAW.2011.2.3.282.
MA-HOCK L, STRAUSS V, TREUMANN S, et al . Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black[J ] . Part Fibre Toxicol, 2013, 10(1): 23. DOI: 10. 1186/1743-8977-10-23.
ZHANG R, DAI Y, ZHANG X, et al . Reduced pulmonary function and increased pro-inflammatory cytokines in nanoscale carbon black-exposed workers[J ] . Part Fibre Toxicol, 2014, 11(1): 73. DOI: 10.1186/s12989-014-0073-1.
DAI Y, NIU Y, DUAN H, et al . Effects of occupational exposure to carbon black on peripheral white blood cell counts and lymphocyte subsets[J ] . Environ Mol Mutagen, 2016, 57(8): 615-622. DOI:10.1002/em.22036.
李园园, 高峰, 解秋艳, 等.吸入染毒纳米级炭黑气溶胶致小鼠肺炎性损伤的研究[J].中华预防医学杂志, 2014, 48(12): 1098-1103.DOI:10.3760/cma.j.issn.0253-9624.2014.12.016.
LI Y Y, GAO F, XIE Q Y, et al . Study on the pulmonary inflammatory effects induced by inh alation exposure to nanoscale carbon black aerosol in mice[J ] . Chin J Prev Med, 2014, 48(12): 1098-1103. DOI: 10. 3760/cma.j.issn.0253-9624.2014.12.016.
BOURDON J A, SABER A T, JACOBSEN N R, et al . Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver[J ] . Part Fibre Toxicol, 2012, 9(1): 5. DOI: 10.1186/1743-8977-9-5.
FRAMPTON M W. Systemic and cardiovascular effects of airway injury and inflammation: ultrafine particle exposure in humans[J]. Environ Health Perspect, 2001, 109(Suppl 4): 529-532. DOI: 10.2307/3454664.
SAHU D, KANNAN G M, VIJAYARAGHAVAN R. Carbon black particle exhibits sizedependent toxicity in human monocytes[J]. Int J Inflam, 2014, 2014: 827019. DOI: 10. 1155/2014/827019.
STOEGER T, REINHARD C, TAKENAKA S, et al . Instillation of six different ultrafine carbon particles indicates a surface area threshold dose for acute lung inflammation in mice[J ] . Environ Health Perspect, 2006, 114(3): 328-333. DOI: 10.1289/ehp.8266.
KIM Y M, REED W, LENZ A G, et al . Ultrafine carbon particles induce interle ukin-8 gene transcription and p38 MAPK activation in normal human bronchial epithelial cells[J ] . Am J Physiol Lung Cell Mol Physiol, 2005, 288(3): 432-441. DOI: 10.1152/ajplung.00285.2004.
HUSAIN M, KYJOVSKA Z O, BOURDON-LACOMBE J, et al . Carbon black nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 mice following a single intratracheal instillation[J ] . Toxicol Appl Pharmacol, 2015, 289(3): 573-588. DOI: 10.1016/j.taap.2015.11.003.
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