纳米二氧化硅致大鼠肺组织损伤的病理动态变化

Dynamic changes of pathological morphology and ultrastructure of lung injury in rats induced by SiO2 nanoparticles

目的 观察纳米SiO2对大鼠的肺损伤作用.方法 150只雄性SD大鼠分为生理盐水对照组、6.25、12.5、25 mg/ml纳米SiO2和25 mg/ml微米SiO2组,每组30只,分别观察7、15、30、60、90 d后,各处死6只大鼠,计算肺脏脏器系数、观察肺组织病理形态及超微结构改变.结果 在各染尘时间点,25 mg/ml微米SiO2组与纳米SiO2组大鼠肺脏器系数明显高于生理盐水组,25 mg/ml微米SiO2组大鼠肺脏器系数明显高于同剂量纳米SiO2组,差异均有统计学意义（P＜0.05）.微米SiO2组肺脏器系数增加,各剂量纳米SiO2组大鼠肺脏器系数降低,呈现时间-效应关系.光学显微镜下可见微米SiO2组随着染尘时间的延长,肺内逐渐形成细胞性结节并融合成细胞纤维性结节;25 mg/ml纳米SiO2组染尘早期呈局灶性肺泡巨噬细胞聚集和纤维母细胞增生,后期则出现纤维结缔组织增生.透射电镜下可见25mg/ml微米SiO2组及纳米SiO2组Ⅱ型肺泡上皮细胞嗜锇板层小体异常,间质中胶原及弹力纤维增生.结论 纳米SiO2颗粒暴露可致大鼠肺组织损伤,早期以炎症为主,后期则主要表现为肺间质纤维化,不同于微米SiO2所致结节性肺纤维化,其致纤维化能力较同浓度微米SiO2弱.

Objective To observe the lung injury in rats induced by SiO2 nanoparticles.Methods One hundred and fifty SD rats were divided into five groups：the control group,the nanosized SiO2 groups of 6.25、12.5,25 mg/ml,and the microsized SiO2 group of 25 mg/ml,30 rats each group.On the 7th,15th,30th,60th and 90th day after exposure,six rats were sacrificed at each time point and the lung viscera coefficient,the pathological morphology and ultrastructure of lung were observed.Results At each time point,the rat lung viscera coefficient of 25 mg/ml microsized SiO2 and nanosized SiO2 group were higher than the physiological saline group （P〈0.05）,25 mg/ml microsized SiO2 group was higher than the same dose of nanosized SiO2 group （P〈0.05）; With longer duration of dye dust,lung viscera coefficient of 25 mg/ml microsized SiO2 group and each dose of nanosized SiO2 group were in time-effect relationship.Under light microscope we can see microsized SiO2 group gradually formed cellularity nodules,and fused into fibrous nodules; At the early stage 25 mg/ml nanosized SiO2 group occured focal alveolar macrophages and fibroblast proliferation and later fibrous connective tissue proliferated.Under TEM osmium lamellar corpuscle of type Ⅱ alveolar epithelial cells were abnormal,and collagen and elastic fiber proliferated in mesenchyme of microsized and nanosized SiO2 group.Conclusion Nanosized SiO2 particles after exposure can cause lung tissue injury in rat,and at the early stage it is showed inflammation,and later mainly characterized by pulmonary interstitial fibrosis differing from nodular lung fibrosis caused by microsized SiO2,its ability to fibrosis is weaker compared with the same concentration of microsized SiO2.