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
Effects of Nano-titanium Dioxide on Notch Signaling Pathway and Secretion of Inflammatory Factors in Microglia
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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。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.
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Key words:
- titanium dioxide nanoparticles /
- microglia /
- inflammation /
- inflammatory factors /
- Notch
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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):67-69 Zhao 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 -
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