张小强,,
李琪,
孙腾腾,
崔丹丹
环境医学工程教育部重点实验室, 东南大学公共卫生学院, 南京 210000
作者简介: 陶一凡(1995-),男,硕士研究生,研究方向为食品毒理学和纳米毒理学,E-mail:670581814@qq.com.
通讯作者: 张小强,zhangxq7843@126.com ;
基金项目: 江苏省普通高校研究生科研创新计划资助项目（SJZZ16_0034）中图分类号: X171.5
Effects of Nano-titanium Dioxide on Notch Signaling Pathway and Secretion of Inflammatory Factors in Microglia
Tao Yifan,Zhang Xiaoqiang,,
Li Qi,
Sun Tengteng,
Cui Dandan
Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210000, China
Corresponding author: Zhang Xiaoqiang,zhangxq7843@126.com ;
CLC number: X171.5
-->
摘要
HTML全文
图
参考文献
相关文章
施引文献
资源附件
访问统计
摘要:由于纳米材料的广泛应用及其可能存在的生物安全性风险，本研究探讨了纳米二氧化钛对小胶质细胞Notch信号通路及炎症因子分泌水平的影响。以不同浓度的纳米二氧化钛染毒小胶质细胞，MTT法测定细胞活力，乳酸脱氢酶（LDH）检测试剂盒测定细胞培养液上清液LDH活性，ELISA法测定细胞培养液上清液肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）的分泌水平，Western Blot法检测Notch-1和Hes-1的蛋白表达水平。结果表明，与对照组相比，纳米二氧化钛40.0 μg·mL-1和50.0 μg·mL-1暴露组细胞活力显著降低；纳米二氧化钛20.0、30.0和40.0 μg·mL-1暴露组LDH水平明显升高；纳米二氧化钛15.0、20.0、30.0和40.0 μg·mL-1暴露组TNF-α、IL-1β和IL-6分泌水平升高；纳米二氧化钛20.0、30.0和40.0 μg·mL-1暴露组Notch-1及Hes-1蛋白表达水平升高。研究表明，纳米二氧化钛暴露导致细胞活力降低，破坏细胞膜的完整性，炎症因子及Notch信号通路相关蛋白Notch-1和Hes-1的表达水平升高。
关键词: 纳米二氧化钛/
小胶质细胞/
炎症反应/
炎症因子/
Notch
Abstract:In consideration of the wide application of nanomaterials and the potential risk of their biosafety, this study aimed to investigate the effects of Nano-TiO2 on Notch signaling pathway and the secretion of inflammatory factors in microglia. Different concentrations of Nano-TiO2 were used to intervene microglia cells. The cell viability was determined by MTT; the lactate dehydrogenase (LDH) detection kit was used to determine LDH activity in the cell supernatant; the secretion level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the cell supernatant were measured by ELISA; the protein expression levels of Notch-1 and Hes-1 were detected by Western Blotting. Compared with the control group, the cell viability of the 40.0 μg·mL-1 and 50.0 μg·mL-1 Nano-TiO2 exposure group was significantly reduced; 20.0, 30.0 and 40.0 μg·mL-1 Nano-TiO2 exposure group had a significant increase in LDH level; the secretion levels of TNF-α, IL-1β and IL-6 were increased in the 15.0, 20.0, 30.0 and 40.0 μg·mL-1 Nano-TiO2 exposure groups; the expression levels of Notch-1 and Hes-1 were increased in the 20.0, 30.0 and 40.0 μg·mL-1 Nano-TiO2 exposure groups. It is suggested that the exposure of Nano-TiO2 lead to the decrease of cell viability, the destruction of cell membrane integrity, and the increase on the expression of inflammatory factors, Notch-1 and Hes-1 proteins.
Key words:titanium dioxide nanoparticles/
microglia/
inflammation/
inflammatory factors/
Notch.
| Wang L Z, Sasaki T. Titanium oxide nanosheets:Graphene analogues with versatile functionalities[J]. Chemical Reviews, 2014, 114(19):9455-9486 |
| Venkatasubbu G D, Baskar R, Anusuya T, et al. Toxicity mechanism of titanium dioxide and zinc oxide nanoparticles against food pathogens[J]. Colloids and Surfaces B:Biointerfaces, 2016, 148:600-606 |
| Wang Y N, Ma J Z, Xu Q N, et al. Fabrication of antibacterial casein-based ZnO nanocomposite for flexible coatings[J]. Materials & Design, 2017, 113:240-245 |
| Kubacka A, Serrano C, Ferrer M, et al. High-performance dual-action polymer-TiO2 nanocomposite films via melting processing[J]. Nano Letters, 2007, 7(8):2529-2534 |
| 赵秋艳, 李汴生. 新型铁营养强化剂——超微细元素铁粉[J]. 食品与发酵工业, 2001, 27(6):67-69Zhao Q Y, Li B S. A new iron dietary supplement-ultramicro iron powder[J]. Food and Fermentation Industries, 2001, 27(6):67-69(in Chinese) |
| Kumar P, Mahajan P, Kaur R, et al. Nanotechnology and its challenges in the food sector:A review[J]. Materials Today Chemistry, 2020, 17:100332 |
| Lim J H, Bae D, Fong A. Titanium dioxide in food products:Quantitative analysis using ICP-MS and Raman spectroscopy[J]. Journal of Agricultural and Food Chemistry, 2018, 66(51):13533-13540 |
| Grissa I, Guezguez S, Ezzi L, et al. The effect of titanium dioxide nanoparticles on neuroinflammation response in rat brain[J]. Environmental Science and Pollution Research, 2016, 23(20):20205-20213 |
| Long T C, Tajuba J, Sama P, et al. Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro[J]. Environmental Health Perspectives, 2007, 115(11):1631-1637 |
| Song B, Liu J, Feng X L, et al. A review on potential neurotoxicity of titanium dioxide nanoparticles[J]. Nanoscale Research Letters, 2015, 10(1):1042 |
| Chen I C, Hsiao I L, Lin H C, et al. Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability[J]. Environmental Toxicology and Pharmacology, 2016, 47:108-118 |
| Butovsky O, Weiner H L. Microglial signatures and their role in health and disease[J]. Nature Reviews Neuroscience, 2018, 19(10):622-635 |
| Kettenmann H, Hanisch U K, Noda M, et al. Physiology of microglia[J]. Physiological Reviews, 2011, 91(2):461-553 |
| Cheng M, Yang L, Dong Z P, et al. Folic acid deficiency enhanced microglial immune response via the Notch1/nuclear factor kappa B p65 pathway in hippocampus following rat brain I/R injury and BV2 cells[J]. Journal of Cellular and Molecular Medicine, 2019, 23(7):4795-4807 |
| Rihane N, Nury T, M'rad I, et al. Microglial cells (BV-2) internalize titanium dioxide (TiO2) nanoparticles:Toxicity and cellular responses[J]. Environmental Science and Pollution Research, 2016, 23(10):9690-9699 |
| Valentini X, Deneufbourg P, Paci P, et al. Morphological alterations induced by the exposure to TiO2 nanoparticles in primary cortical neuron cultures and in the brain of rats[J]. Toxicology Reports, 2018, 5:878-889 |
| Wang Y C, He F, Feng F, et al. Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses[J]. Cancer Research, 2010, 70(12):4840-4849 |
| Wu F, Luo T, Mei Y W, et al. Simvastatin alters M1/M2 polarization of murine BV2 microglia via Notch signaling[J]. Journal of Neuroimmunology, 2018, 316:56-64 |
| Grandbarbe L, Michelucci A, Heurtaux T, et al. Notch signaling modulates the activation of microglial cells[J]. Glia, 2007, 55(15):1519-1530 |
| Song B, Zhou T, Yang W L, et al. Contribution of oxidative stress to TiO2 nanoparticle-induced toxicity[J]. Environmental Toxicology and Pharmacology, 2016, 48:130-140 |
| Zhang R, Niu Y J, Li Y W, et al. Acute toxicity study of the interaction between titanium dioxide nanoparticles and lead acetate in mice[J]. Environmental Toxicology and Pharmacology, 2010, 30(1):52-60 |
| Hughes V. Microglia:The constant gardeners[J]. Nature, 2012, 485(7400):570-572 |
| Cao Q, Lu J, Kaur C, et al. Expression of Notch-1 receptor and its ligands Jagged-1 and Delta-1 in amoeboid microglia in postnatal rat brain and murine BV-2 cells[J]. Glia, 2008, 56(11):1224-1237 |
