不同粒径的介孔纳米硅材料皮下给予小鼠的急性毒性  

Acute toxicities of mesoporous silica nanoparticles of different size in mice

作　　者：席晨[1] 王周华[2] 付新录[3] 黄芝瑛[1,3] 

机构地区：[1]中山大学药学院药物安全评价中心,广东广州510006 [2]中山大学药学院药剂实验室,广东广州510006 [3]中山大学药学院实验动物中心,广东广州510006

出　　处：《中国药理学与毒理学杂志》2014年第1期68-73,共6页Chinese Journal of Pharmacology and Toxicology

基　　金："十一五"国家科技支撑计划重点项目(2008BAI55B03)~~

摘　　要：目的研究介孔纳米硅材料(MSN)经皮下注射对小鼠的急性毒性,分析异常反应与材料粒径的关系,探讨诱发局部刺激及全身毒性的相关机制。方法昆明小鼠一次性sc给予MSN 1000 mg·kg-1的3种不同颗粒(80,200,1000 nm)和粒径约20 nm的二氧化硅纳米粉末(NP)。14 d后取血进行血液学检测,称重并计算心、肝、脾、肺和肾脏器系数,制片并进行病理组织学检查。结果 80 nm和1000 nm的MSN和NP会导致小鼠皮下出现肉眼可见的肿块,出现肿块的时间顺序和严重程度为20 nm NP>1000 nm>80 nm。此外,其均会不同程度地诱发小鼠皮下注射部位纤维组织增生和炎症细胞浸润,并引起肝细胞水肿和脾生发中心变大等,血液中白细胞和血小板量均显著性地增加(P<0.05)。200 nm的MSN未导致动物出现皮损,且病理观察和血液学指标的异常程度均低于其他给药组。结论皮下注射不同粒径的MSN会导致小鼠产生刺激性毒性,并且这种毒性与颗粒粒径相关,皮下刺激毒性的严重程度为20 nm NP>1000 nm>80 nm>200 nm。OBJECTIVE To investigate the acute toxicity of mesoporous silica nanoparticles（ MSN） by subcutaneous injection in mice,and to analyze the relationship between abnormal reactions and particle sizes. METHODS A single dose 1000 mg·kg^-1 of MSN 80,200 and 1000 nm and silica nanoparticles（ NP） was injected via sc to Kunming mice. A 14-day observation period was set with the general reactions recorded. At the end of the observation period,the mice were sacrificed after their blood sample was taken and their heart,liver,spleen,lung,and kidneys were removed. The wet mass and relative mass of the above organs were calculated before the hemalogical and pathological examination was performed. RESULTS Nanoparticles of 20 nm NP and MSN of 80 nm and 1000 nm induced visible swelling in mice. Swelling occurred first and was most severe in 20 nm NP group,followed by 1000 nm and 80nm groups. NP and MSN mentioned above also led to tosubcutaneous fibrous tissue proliferation and inflammatory cell infiltration,and liver cell edema and splenic germinal center became larger. In the hematological examination,the white blood cell and platelet count were significantly increased（ P 0. 05）. In contrast,during the observation period,MSN with 200 nm didn＇t cause any skin lesions and pathological observations. The abnomality of hematological indexes were less than in other treated groups. CONCLUSION MSN of different sizes can induce irritation and inflammation in mice,and the injury depends on the particle size. The skin acute toxicity is most severe in 20 nm NP groups,followed by 1000,80 and 200 nm groups.

关 键 词：纳米粒子 硅 粒径 急性毒性实验 

分 类 号：R318.08[医药卫生—生物医学工程]