大气细颗粒物吸入动物模型建立及适用性评价
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福建省实验动物研究科技计划重点项目(2013Y0085);福建省科技计划引导性项目(2015Y0004)。


Establishment and evaluation of animal model induced by inhalation injury of airborne fine particulate matter
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    摘要:

    目的 建立大气细颗粒物(PM2.5)气溶胶慢性吸入致机体损伤的动物模型。方法 制备PM2.5气溶胶连续吸入装置。分别考察不同浓度(100±10 μg/m3、150±10 μg/m3、200±10 μg/m3)、不同时间(1周、2周、4周、8周、12周)、不同方法(非暴露气管内灌注法和气溶胶吸入法)和不同动物(Wistar大鼠、BN大鼠和豚鼠)对模型建立的影响。观察动物一般状态并计算体重增长率与死亡率;检测肺功能包括呼吸频率、用力呼气量占用力肺活量比值(FEV1/FVC)与动脉氧分压(PO2);计数支气管肺泡灌洗液(BALF)细胞分类;光镜检查气管、肺组织病理。以气管、肺组织病理可见到肺炎为建立成功模型标准,确定建立模型的影响因素。结果 不同浓度PM2.5气溶胶连续吸入8周,Wistar大鼠出现中毒现象,体重增长缓慢,支气管肺泡灌洗液(BALF)中白细胞总数和单个核细胞计数增加、巨噬细胞比率上升,肺功能指标中呼吸频率增高、动脉血 PO2和 FEV1/FVC降低,病理示气管、肺组织出现炎症及肺纤维化变化,炎症变化与染毒浓度呈正相关但高浓度死亡率高。持续不同时间(1周、2周、4周、8周和12周)吸入相同浓度,Wistar大鼠染毒动物气管肺组织病变8周起显著但与12周无差异。不同方法(非暴露气管内灌注法和气溶胶吸入法)Wistar大鼠连续吸入8周,两法染毒效果相当但吸入法动物死亡率低。Wistar大鼠、BN大鼠和豚鼠不同动物连续吸入8周,三种动物效果相当但Wistar大鼠死亡率低。结论 选用Wistar大鼠吸入浓度为150±10 μg/m3的PM2.5气溶胶连续8周可建立合适的PM2.5致机体损伤动物模型,研究制备一个与PM2.5损伤机体相似的致病环境,率先建立既适合全国大范围,同时具有福建地区特点PM2.5致机体损伤动物的模型,将促进PM2.5预防与治疗措施研究的开展。

    Abstract:

    Objective To establish and evaluate the animal model induced by inhalation injury of airborne fine particulate matter (PM2.5). Methods We manufactured equipment for rats aerosol inhalation with PM2.5. The effects of several facters such as concentrations(100±10 μg/m3、150±10 μg/m3、200±10 μg/m3)、time(1w、2w、4w、8w、12w)、method (non-exposed intratracheal instillation method and aerosol inhalation) and animals (Wistar rats, BN rats and guinea pigs) were investigated to establish the model. The respiratory rate, forced vital capacity ratio of forced expiratory volume (FEV1/FVC) and arterial partial pressure of oxygen (PO2) were measured, the pathological changes of bronchial and lung tissues under light microscope were observed. The success animal model was builded as the pneumonia was observed from the pathological changes of lung tissue. Results The Wistar rats exposed to PM2.5 aerosol inhalation for 8 weeks, we can see that the weight growth rate of rat decreased, WBC count and mononuclear cells count increased, the macrophages ratio decreased in BALF, the respiratory rate of lung increased while arterial PO2 and FEV1/FVC decreased, inflammation and pulmonary fibrosis changes were observed by bronch and pulmonary pathology, inflammatory changes with a dose-response relationship were observed. Exposed to PM2.5 aerosol inhalation for different time(1 w、2 w、4 w、8 w、12 w)with same dose, the score issue lesions of lung and bronchus in Wistar rats increased and the 8w group is obvious. The Wistar rats exposed to PM2.5 with different method (aerosol inhalation and non-exposed intratracheal instillation method) for 8w, the aerosol inhalation worked as effectively as perfusion while mortality rate of aerosol inhalation is lower. Different animals (Wistar rats, BN rats and guinea pigs) exposed to PM2.5 aerosol inhalation for 8w, the same results were observed with three method respectively while mortality rate of Wistar rats lower. Conclusions The optional conditions that the Wistar rats were continuously inhaled for 8w PM2.5 with a dose of 150±10 μg/m3 were established. The animal model could be used on a national scale, especially in Fujian province. The results would be useful for the development of the research of the prevention and countermeasures of PM2.5 pollution.

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邓元荣,李泳宁,黄晓敏,徐驯宇.大气细颗粒物吸入动物模型建立及适用性评价[J].中国比较医学杂志,2016,26(9):42~49.

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  • 最后修改日期:2016-04-01
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  • 在线发布日期: 2016-09-22
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