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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