SiO2纳米颗粒暴露致新生小鼠皮层应激及炎症反应的实验研究

Effects of silica nanoparticles exposure on cortical stress and neuroinflammation in neonatal mice

目的研究SiO_2纳米颗粒(SiO_2-NPs)暴露对新生小鼠大脑皮层应激及炎症反应的影响,探讨SiO_2-NPs的神经毒性机制。方法选取新生小鼠随机分3组:低剂量组、高剂量组和对照组。小鼠出生后第1天(P1)至P7各组每天分别接受SiO_2-NPs溶液10 mg/3 ml、50 mg/3 ml或等体积生理盐水雾化暴露30 min。P8时采用免疫组织化学法检测皮层糖皮质激素受体(GR)、星形胶质细胞标志物(GFAP)及小胶质细胞标志物(Iba1)的表达,ELISA检测皮层炎症因子IL-6、TNF-α、IL-1β的水平。结果高剂量组皮层GR阳性细胞数明显高于对照组(P<0.05);高剂量组与低剂量组皮层Iba1阳性细胞数量均明显多于对照组(P<0.01,P<0.05),活化明显;高剂量组皮层GFAP阳性细胞数量多于对照组、低剂量组(P<0.01,P<0.05);随SiO_2-NPs暴露剂量增加,皮层炎症因子TNF-α、IL-6、IL-1β均有上调。结论 SiO_2-NPs暴露可使新生小鼠皮层产生应激和炎症反应,且高剂量SiO_2-NPs暴露的神经毒性效应更显著。

The study aimed to investigate the effects of silica nanoparticles （SiO2-NPs） on cortical stress and neuroinflammation in neonatal mice, and explore the possible mechanisms of SiO2-NPs neurotoxicity. Neonatal mice were randomly divided into three groups： low dose （10 mg/3 ml）, high dose SiO2-NP-treatment group （50 mg/3 ml） and control group. From postnatal day 1 （P1） to P7, mice were treated with SiO2-NP suspension 10 mg/3 ml, 50 rag/3 ml or 3 ml normal saline by aerosol inhalation respectively, 30 rain per day. Immunohistochemistry techniques were used to detect the expression of glueocorticoid receptor （GR）, ionized calcium binding adapter molecule 1 （Ibal） and glial fibrillary acidic protein （GFAP） in the cerebral cotex of mice on PS; ELISA was used to measure the concentration of IL-6, TNF-α, and IL-1β in cortex. Data showed that the expression of GR in cortex of high dose SiO2-NP-treatment group was significantly increased, as compared to control group （P〈0.05）. Compared to the control group, microglia in cortex of low dose and high dose SiO2-NP-treatment group were both significantly increased （P〈0.05, P〈0.O1）. And the number of cortical GFAP-labeled astrocytes of high dose SiO2-NP-treatment group was significantly higher than that of control group and low dose SiO2-NP-treatment group （P〈0.01, P〈0.05）. Furthermore, the expression of inflammatory cytokines TNF-α, IL-6, IL-1β were all up-regulated with the increased dose of SiO2-NP exposure, as compared to control group. In conclusion, SiO2-NP exposure in neonatal mice results in cortical stress and neuroinflammatory response, and neurotoxicity of high dose SiO2-NP exposure is more obvious in cortex of neonatal mice.