不同暴露时间TiO_2纳米粒子对雌性小鼠脑单胺类神经递质的影响

Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic neurotransmitters of female mice at different exposure time

目的探讨小鼠鼻腔滴注二氧化钛（TiO2）纳米粒子对脑中单胺类神经递质的影响。方法以50mg／kg的剂量给CD雌性小鼠隔天鼻腔滴注不同粒径大小的TiO：（25、80和155nm）水悬浮液（浓度为10^5mg／L），同时设定对照组。分别在暴露2、10、20和30d后用电感耦合等离子体质谱仪分析小鼠脑组织中钛元素的含量，采用反相高效液相色谱-电化学检测法测定暴露20和30d后小鼠脑中单胺类神经递质的含量。结果在暴露10d时，小鼠脑中钛的含量上升较快，25nm组小鼠脑中钛的含量即达到（1059．3±293.5）ng／g；在暴露20d之后，脑中钛的含量有一定降低，仍维持在较高水平，25nm组中钛的含量下降为（654.7±269．2）ng／g。暴露30d时钛含量没有明显改变。由于吸入的TiO2粒子在小鼠脑中的蓄积，导致80nm和155nm组中小鼠脑中去甲肾上腺素（NE）和5-羟色胺（5-HT）含量在暴露20d时明显升高，而多巴胺（DA）、3、4-双羟苯乙酸（DOPAC）、高香草酸（HVA）和5-羟吲哚乙酸（5-HIAA）的含量有一定下降。结论吸入的TiO2颗粒可以经鼻黏膜吸收入脑并能蓄积于小鼠的脑组织中，影响脑中单胺类神经递质的代谢。

Objective To investigate the influence of intranasal instilling titanium dioxide （ TiO2 ） nanoparticles on monoaminergic neurotransmitters at different-time exposure. Methods CD female mice were intranasally instilled three different-sized （25 nm, 80 nm and 155 nm） TiO2 suspension every other day in a dose of 50 mg/kg body weight. The control group was instilled the same volume of Milli-Q water. Inductively coupled plasma-mass spectrometry （ICP-MS） was used to analyze the titanium contents in murine brain after exposure to TiO2 particles 2 days, 10 days, 20 days and 30 days. The monoaminergic neurotransmitters such as norepinephrine （ NE ）, dopamine （ DA ）, 5-hydroxytryptamine （ 5-HT ）, 5-hydroxyindole acetic acid （5-HIAA）, 3, 4-dihydroxyphenylacetic acid （DOPAC）, and homovanillic （HVA）, were determined by reversed-phase high performance liquid chromatography （RP-HPLC） with electrochemical detector. Results After exposure to TiO2 nanoparticles 10 days, the titanium contents in murine brain were increased, the titanium content in the 25 nm group was up to （1059. 3 ＋- 293.5） ng/g. In 20 days, the titanium content decreased slowly with the metabolism of titanium in vivo, but it kept at a high level, the content decreased to （654. 7 ＋- 269.2 ） ng/g in the 25 nm group. After exposure to TiO2 nanoparticles 30 days, the titanium contents had no obviously change. Because of the accumulation of TiO2 in the brain, the contents of NE and 5-HT increased significantly after exposure to 80 nm and 155 nm TiO2 nanoparticles 20 days, while the decreased contents of DA, DOPAC, HVA and 5-HIAA were observed. Conclusion The inhaled TiO2 nanoparticles could be translocated to and deposited in murine brain after absorbing by nasal mucosa, and further influence the releases and metabolisms of monoaminergic neurotransmitters in brain.