Medical College of Soochow University, Suzhou 215123, China.
Library of Soochow University, Suzhou 215123, China.
J Hazard Mater. 2014 Aug 15;278:180-8. doi: 10.1016/j.jhazmat.2014.06.005. Epub 2014 Jun 12.
Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various areas, and its potential toxicity has gained wide attention. However, the molecular mechanisms of multiple genes working together in the TiO2 NP-induced splenic injury are not well understood. In the present study, 2.5, 5, or 10mg/kg body weight TiO2 NPs were administered to the mice by intragastric administration for 90 consecutive days, their immune capacity in the spleen as well as the gene-expressed characteristics in the mouse damaged spleen were investigated using microarray assay. The findings showed that with increased dose, TiO2 NP exposure resulted in the increases of spleen indices, immune dysfunction, and severe macrophage infiltration as well as apoptosis in the spleen. Importantly, microarray data showed significant alterations in the expressions of 1041 genes involved in immune/inflammatory responses, apoptosis, oxidative stress, stress responses, metabolic processes, ion transport, signal transduction, cell proliferation/division, cytoskeleton and translation in the 10 mg/kg TiO2 NP-exposed spleen. Specifically, Cyp2e1, Sod3, Mt1, Mt2, Atf4, Chac1, H2-k1, Cxcl13, Ccl24, Cd14, Lbp, Cd80, Cd86, Cd28, Il7r, Il12a, Cfd, and Fcnb may be potential biomarkers of spleen toxicity following exposure to TiO2 NPs.
二氧化钛纳米粒子（TiO2 NPs）已广泛应用于各个领域，其潜在毒性引起了广泛关注。然而，TiO2 NP 诱导的脾脏损伤中多个基因协同作用的分子机制尚不清楚。在本研究中，通过灌胃方式给小鼠连续 90 天施用 2.5、5 或 10mg/kg 体重的 TiO2 NPs，利用微阵列分析检测其脾脏中的免疫能力以及受损脾脏中的基因表达特征。结果表明，随着剂量的增加，TiO2 NP 暴露导致脾脏指数增加、免疫功能障碍以及巨噬细胞浸润和脾脏细胞凋亡严重。重要的是，微阵列数据分析显示，10mg/kg TiO2 NP 暴露的脾脏中，有 1041 个参与免疫/炎症反应、细胞凋亡、氧化应激、应激反应、代谢过程、离子转运、信号转导、细胞增殖/分裂、细胞骨架和翻译的基因表达发生显著改变。具体而言，Cyp2e1、Sod3、Mt1、Mt2、Atf4、Chac1、H2-k1、Cxcl13、Ccl24、Cd14、Lbp、Cd80、Cd86、Cd28、Il7r、Il12a、Cfd 和 Fcnb 可能是 TiO2 NPs 暴露后脾脏毒性的潜在生物标志物。
