纳米级二氧化硅粉尘引起小鼠急性肺损伤的实验研究

目的探讨二氧化硅纳米颗粒引起的小鼠急性肺损伤效应。方法将48只C57BL/6小鼠(雌雄各半)随机分成2组,实验组经气管滴入SiO2混悬液,对照组滴入生理盐水。第1天、7天、14天、21天,各组分别处死6只小鼠,收集支气管肺泡灌洗液(BALF),计数有核细胞总数并分类。取左肺组织,固定、切片后行HE染色,观察组织病理改变,进行半定量评分。取右肺组织,称重,干燥后计算肺组织湿干重比。结果实验组小鼠染矽后的第1天、7天、14天、21天,BALF细胞总数、肺组织病理分值均显著高于对照组(P<0.01),肺湿干重比数值高于对照组(P<0.05)。与染矽第1天小鼠比较,染矽第7天和第14天小鼠BALF细胞总数明显增多(P<0.01);染矽第7天小鼠BALF中,中性粒细胞比例增多(P<0.05),淋巴细胞比例减少(P<0.05);染矽第7天、14天和21天小鼠肺组织病理分值和肺湿干重比明显上升(P<0.01)。与染矽第7天、14天小鼠比较,染矽第21天小鼠肺组织病理分值以及湿干重比下降(P<0.05)。结论二氧化硅纳米颗粒进入小鼠肺组织后的1¹4 d期间,引起肺组织急性炎症反应,21 d后肺组织炎症反应减弱,损伤趋于慢性化。

Experimental study on acute lung injury induced by nanometer-sized silica particles in mice

Objective To investigate the acute lung injury in mice induced by nanometer-sized silica particles. Methods Forty eight C57BL/6 mice（sex in half） were randomly allocated into test group and control group. The test group mice were through trachea injected with silica suspension or normal saline for control. At 1 d, 7 d, 14 d and 21 d post silica exposure, six mice in each group were sacrificed. After the bronchoalveolar lavage fluid（BALF） were collected, the total nucleated cell were counted and classified.Then, the left lung tissue fixed and stained by HE stain, and the pathological changes were examined to evaluate of scores. The ratio of wet weight to dry weight of right lung was counted. Results At 1 d, 7 d, 14 d and 21 d post silica treatment, the total cells of BALF and the scores of lung pathological changes in test group mice were all obviously more than that in control group mice（P0.01）, and the ratio of wet weight to dry weight for test group was also more than that for control group（P0.05）. Compared with 1 d of mice after silica treatment, the total cells of BALF significantly increased at 7 d and 14 d post silica treatment（P0.01）, the neutrophil proportion increased and the lymphocyte proportion decreased at 7 days post silica treatment（P0.05）, and the scores of lung pathological changes and the ratio of wet weight to dry weight obviously increased at 7 d, 14 d and 21 d post silica treatment（P0.01）. Compared with 7 d and 14 d of mice after silica treatment, the scores of lung pathological changes and the ratio of wet weight to dry weight obviously reduced at 21 d post silica treatment（P0.05）. Conclusion Afternanometer-sized silica particles entering lung of mice, the acute lung inflammatory reaction happen in mice during 1 day to 14 days, and the inflammatory reaction weaken and tend to chronic injury after 21 days.