纳米二氧化钛损伤小鼠皮肤的机制研究

The Mechanism of Nano-titanium Dioxide-induced Mice Dermal Toxicity

目的拟用基因芯片技术研究纳米二氧化钛作用皮肤组织的分子机制,用于预防皮肤损伤和安全性评价研究。方法取ICR雌性小鼠(24±2)g,随机分为3个供试组和1个空白对照组,每组12只。在已刮取毛发的小鼠背部分别涂抹锐钛型10 nm、金红石型25 nm和P25混合型3种规格的纳米二氧化钛混悬液,空白对照小鼠涂抹纯化水每日1次,持续5周。试验结束后,提取小鼠皮肤中RNA,利用基因芯片技术筛选供试组和空白对照组小鼠表达差异基因,利用在线数据库工具对表达差异基因进行分类和富集。结果锐钛型(10 nm)主要影响细胞分化、细胞黏附和膜稳定性,金红石型(25 nm)和P25对细胞免疫微环境有影响。蛋白互作分析显示Mta1,Trp53,Fos,25 Sox2,Nanog,and Kmt2d是纳米二氧化钛作用皮肤细胞的关键分子。结论本研究显示相同剂量不同晶型和粒径的纳米二氧化钛对皮肤作用机制不同,纳米二氧化钛在医药领域的应用亟需新的安全评价方法。

OBJECTIVE To identify the molecular mechanism of the mice skin upon nano-TiO2 by gen chip technology for preventing the skin injury and safety evalution.METHODS 48 healthy female ICR mice(24±2)g were divided into three treated groups and one control group,which were treated with different crystal forms and sizes(anatase 10 nm,rutile 25 nm,and anatase/rutile P25)of nano-TiO2 through dermal exposure each day for 5 weeks.RNA was extracted from the processed mice skin of treated and control groups and compared via microarrays.The data obtained were analyzed using the online tool Database for Annotation,Visualization,and Integrated Discovery(DAVID)and the data visualization tool Cytoscape.The enriched signaling pathways,biochemical processes,and key genes were identified.RESULTS Anatase 10 nm exerted a very strong influence on stem cell development,cell migration,and mitochondrial apoptotic pathways,while rutile 25 nm and P25 mainly affected immunosuppressive processes.Data revealed six potential key genes regulated by nano-TiO2 treatment,namely Mta1,Trp53,Fos,25 Sox2,Nanog,and Kmt2d.CONCLUSION The three tested forms of nano-TiO2 particles promote different effects.This study enhances of the mechanism underlying 26 nano-TiO2-induced dermal toxicity.