论文总字数：10692字

摘 要

：近年来，经国内外研究表明, 纳米TiO₂对动物中枢神经系统产生毒性作用，其可诱导损伤小鼠脑海马组织、降低其学习记忆能力等，然而是否涉及到轴突或树突发育的抑制及分子机制尚不明朗确。据此，本论文以不同剂量（1.25、2.5、5 mg/kgBW）的纳米TiO₂从孕 0天起孕期和哺乳期对母鼠连续染毒，产后 3 周停止哺乳, 对仔鼠海马组织病理学进行评估，研究纳米TiO₂致仔鼠海马损伤的分子机制。结果显示，经纳米TiO₂染毒组断乳的仔鼠脑脏器系数显著低于对照组，且呈剂量依赖性。仔鼠海马区显示纳米TiO₂颗粒聚集，海马组织病变如神经元细胞凋亡，神经元树突丝长度、分支和树突棘数和密度明显减少，海马组织ERK1/2、p38和JNK 蛋白表达及其磷酸化水平明显增加。由此我们认为，纳米TiO₂可通过血胎屏障进入仔鼠海马，引起仔鼠树突发育抑制，且与ERK1/2/MAPK信号通路活化有关。

关键词：纳米TiO₂母体暴露；仔鼠；海马；树突发育；ERK1/2/MAPK信号通路

Titanium dioxide-induced inhibition of dendritic development involves ERK1/2/MAPK signaling pathways

Abstract：In recent years, numerous studies showed that the nano TiO₂ exposure resulted in central nervous system toxicity on animals, such as brain damages, learning and memory reduction, but whether it is involved in axonal- or dendritic-suppression and molecular mechanisms remains unclear. In this paper, Pregnant mice were intragastrically administered different doses (1.25, 2.5, 5 mg/kgBW) nano-TiO₂ consecutively from 0 days of pregnancy and stop lactation for 3 weeks. The results showed that the brain coefficients of the weaned offspring mice in the nano TiO₂ exposure groups were lower than control in dose dependent manner. The hippocampi showed the aggregation of nano TiO₂, which resulted in the histopathological changes of hippocampus (such as neuron apoptosis), the reductions of length of the dendritic filament, the number and density of dendritic spines and dendrites. Furthermore, nano TiO₂ increased expressions of ERK1/2, p38, and JNK protein and their phosphorylation levels in the hippocampus. It suggests that nano TiO₂ could enter the hippocampus of offspring mice through the blood-fetal barrier, and inhibit the development of dendrites in the offspring, and is related to the activation of ERK1/2/MAPK signaling pathway.

Key words: Maternal exposure to titanium dioxide nanoparticles; Offspring mice, Hippocampus; Dendritic development; ERK1/2/MAPK signaling pathway

目 录

第一部分：研究背景............................................3

1 .纳米TiO₂的性能与应用.....................................3

2 .纳米TiO₂的体内代谢.......................................3

2 .1TiO₂进入体内途径.....................................3

2 .2TiO₂体内转运.........................................3

3 .纳米TiO₂体内毒性研究.....................................4

3.1纳米TiO₂对肺的影响...................................4

3.2纳米TiO₂对生殖能力的影响.............................5

3.3纳米TiO₂对心脏、肝、肾等组织的影响.....................5

3.4纳米TiO₂对神经组织的影响的影响.......................5

4 .总结与未来展望...........................................8

5 .研究思路.................................................8

6 .本论文创新点.............................................8

参考文献......................................................9

第二部分：纳米氧化钛诱导的仔鼠树突发育抑制涉及ERK1/2/MAPK信号通路.........................................................13

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