BIOLOGICAL EFFECTS OF DIESEL EXHAUST PARTICLES (DEP) .2. ACUTE TOXICITY OF DEP INTRODUCED INTO LUNG BY INTRATRACHEAL INSTILLATION
BIOLOGICAL EFFECTS OF DIESEL EXHAUST PARTICLES (DEP) .2. ACUTE TOXICITY OF DEP INTRODUCED INTO LUNG BY INTRATRACHEAL INSTILLATION
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DOI：
10.1016/0300-483x(94)03013-r
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发表时间：
1995-05-23
期刊：
影响因子：
4.5
通讯作者：
SAGAI, M
中科院分区：
文献类型：
--
作者：
ICHINOSE, T;FURUYAMA, A;SAGAI, M
对支气管肺泡灌洗液（BALF）进行组织病理学检查和细胞学分析，以阐明通过气管内滴注进入ICR小鼠肺部的柴油机尾气颗粒（DEP）的急性毒性。气管内施用活性炭（Norit）作为非致水肿碳颗粒的对照。给予两剂（每只小鼠0.4毫克或0.8毫克）DEP后，肺含水量随着滴注剂量和时间的增加而增加，与给予DEP后24小时的对照动物相比，肺水含量分别增加1.9倍和2.7倍。相比之下，滴注Norit对水含量的增加没有影响。通过滴注 DEP 的小鼠 BALF 中炎症细胞的增加，观察到肺部炎症反应。用 DEP 治疗的小鼠 BALF 中性粒细胞增加的程度比用 Norit 治疗的小鼠大得多。在施用 DEP 后 4 小时内，发现 MB 色素呈浓烈颜色，表明内皮细胞损伤的范围和程度。组织病理学观察，注射DEP 6 h后，电镜下观察到毛细血管内皮细胞破裂、基底膜脱离、坏死、I型肺泡细胞破裂、脱落；注射DEP后18～24 h，可见中性粒细胞涌入肺泡，出现肺泡内出血、血管周围水肿、细支气管细胞肥大。然而，用 0.8 mg DEP 治疗的小鼠中这些现象的严重程度高于用 0.4 mg DEP 治疗的小鼠。给予Norit会导致动物肺泡巨噬细胞增加，中性粒细胞轻微浸润到肺泡气腔和肺泡间隔，但对细支气管没有影响。这些结果可能表明，毛细血管内皮细胞和I型肺细胞的损伤是DEP引起的肺毒性的最早变化，这些细胞损伤导致肺泡水肿和随后的炎症反应。
Histopathological examination and cytological analyses in bronchial alveolar lavage fluids (BALF) were performed to clarify the acute toxicity of diesel exhaust particles (DEP) introduced into the lung of ICR mice by intratracheal instillation. Activated charcoal (Norit) was intratracheally administered as a control for non-oedemagenic carbon particles. After administration of two doses (0.4 mg or 0.8 mg per mouse) of DEP, lung water contents increased with instillation dose and with time and increased 1.9 and 2.7-fold, respectively, compared to control animals 24 h after the administration of DEP. In contrast, the instillation of Norit had no effect on the increase in water contents. An inflammatory response in lungs was observed by an increase of inflammatory cells in BALF from mice instilled with DEP. The degree of increase in neutrophils of BALF from mice treated with DEP was much greater than in mice treated with Norit. An intense color of MB-pigment, which showed the extent and degree of endothelial cell injury, was found up to 4 h after administration of DEP. Histopathologically, the disruption of capillary endothelial cells, the detachment from their basement membrane and necrosis, disruption and desquamation of type I pneumocytes were observed, 6 h after the injection of DEP, by electron microscopy, An influx of neutrophils into alveoli, intra-alveolar hemorrhage, perivascular oedema and bronchiolar cell hypertrophy were detected between 18 and 24 h after DEP administration. However, the magnitude of these appearances was greater in mice treated with 0.8 mg of DEP than in mice treated with 0.4 mg. The administration of Norit caused an increase of alveolar macrophages and slight infiltration of neutrophils into the alveolar air spaces and alveolar septa in the animals and had no effects on the bronchioles. These results may suggest that damage of capillary endothelial cells and type I pneumocytes are the earliest changes of lung toxicities by DEP and these cell injuries lead to alveolar oedema and the subsequent inflammatory response.