摘要：纳米TiO2已被证实对心血管系统有一定的毒性，但其作用机制有待探讨。本文用不同剂量(1。25、2。5和5 mg/kg BW)的纳米TiO2持续滴鼻处理小鼠9个月，研究纳米TiO2对心肌细胞的损伤作用及其作用机制。实验发现纳米TiO2颗粒可进入心肌细胞并在线粒体积累，导致细胞凋亡、线粒体结构和功能破坏。进一步分析表明损伤的心肌细胞膜电势下降、活性氧自由基大量积累、锰超氧化物歧化酶活性和还原性谷胱甘肽含量下降、丙二醛和蛋白质羰基化水平增加；线粒体电子传递链相关酶复合体Ⅰ、复合体Ⅱ、复合体Ⅲ、复合体Ⅳ活性、琥珀酸脱氢酶、NADH氧化酶、离子泵相关的Ca2+-ATP酶、Na+/K+-ATP酶和Ca2+/Mg2+-ATP酶活性下降，同时ATP合成能力减弱；与线粒体介导细胞凋亡有关的因子如细胞色素c、caspase3蛋白表达上调，而抑制凋亡的因子Bcl-2蛋白表达下调。这些结果表明纳米TiO2颗粒长期暴露可导致心肌细胞线粒体结构和功能的破坏。80046

毕业论文关键词：纳米TiO2；心肌细胞；超微结构；氧化应激；酶活性；凋亡因子

Abstract: Exposure to titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated to cause toxic effects for cardiovascular system。 However, the toxic mechanisms are unclear。 In the present study, mice were exposed to TiO2 NPs with different doses (1。25, 2。5, or 5 mg/kg BW) by nasal administration for 9 consecutive months。 The damages of myocardial cells and their mechanisms were investigated。 Our findings suggested that TiO2 NPs were accumulated in the myocardial mitochondria, causing apoptosis, impairments of mitochondrial structure and functions。 Furthermore, exposure to TiO2 NPs can cause reduction of mitochondrial membrane potential, over production of reactive oxygen species (ROS), increases of malondialdehyde and protein carbonyl levels, reductions of reduced glutathione (GSH) content, ATP content, enzymatic activities including mitochondria-related manganese superoxide dismutase (Mn-SOD), complex Ⅰ, complexⅡ, complex Ⅲ, complex Ⅳ, succinatedehydrogenase (SDH) and NADH oxidase (NOX) as well as ion pump-related Ca2+-ATPase, Na+/K+-ATPase and Ca2+/Mg2+-ATPase。 In addition, exposure to TiO2 NPs induced mitochondria-mediated cytokine expression including cytochrome c and caspase 3; whereas decreased Bcl-2 expression in the myocardial cells of mice。 It implies that chronic exposure to TiO2 NPs can induce damages of mitochondrial structure and functions in the myocardial cells for animals or humans。

Key words: Titanium dioxide nanoparticles; Myocardial cells; Ultrastructure; Oxidative stress; Enzymatic activity; Apoptotic cytokines

目录

第一部分 研究背景 5

纳米氧TiO2的生物学效应和毒性研究进展 5

1 纳米氧TiO2的特性及应用 5

2 纳米氧TiO2颗粒进入心肌细胞的方式 5

2。1 皮肤吸收 5

2。2  鼻腔吸入 5

2。3 其他吸入方式 6

3 纳米氧TiO2的生物学毒性 6

3。1 神经毒性 6

3。2 心肌毒性 7

3。3 生殖毒性 7

3。4 肝、肺等其他器官毒性 7

4 研究思路 8

5 本论文创新点 8

第二部分：纳米氧TiO2诱导小鼠心肌细胞线粒体损伤的分子机制 9

1前言