纳米氧化钛致小鼠睾丸氧化损伤涉及Nrf2信号通路的功能紊乱

摘要：纳米氧化钛已被证实对生殖系统有一定毒性，但具体作用机制还需进一步讨论。本文采用不同剂量(1。25、2。5和5 mg/kg BW)的纳米氧化钛连续灌胃处理雄性小鼠90天，研究纳米氧化钛对雄性小鼠睾丸的损伤及其作用机制以及涉及Nrf2信号通路功能紊乱影响。实验结果发现纳米氧化钛颗粒能够通过血睾屏障在睾丸中大量积累，导致睾丸受损和细胞凋亡，如生精管发生空泡化、生精层厚度变薄、睾丸细胞排列不规则等。附睾尾部精子异常，精子畸形率增加，生殖力下降等。本文进一步研究表明纳米氧化钛导致睾丸中ROS大量积累、SOD、GSH-PX、GST活性和GSH下降, 脂质、蛋白质和DNA过氧化;与Nrf-2/AREs通路有关的因子Nrf2及其靶基因产物HO-1、GCLC、NQO1、PKC和PI3K表达显著下降，Keap1表达显著增加。小鼠长期暴露于纳米氧化钛会降低Nrf2表达，这说明纳米氧化钛长期暴露会导致雄性小鼠睾丸损伤以及能涉及Nrf2信号通路功能紊乱。94849

毕业论文关键词：纳米氧化钛；小鼠；睾丸；Nrf2信号通路；氧化损伤

Abstract：Exposed to titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated to cause toxic effects for reproductive system。 However, the toxic mechanisms need further discussion。 In the present study, male mice were exposed to TiO2 NPs with different doses (1。25, 2。5, or 5 mg/kg BW) by gavage administration for 90 days。 The damages of male mice testis and their mechanisms were investigated。 The effect of Nrf2 signal pathway functional disorder was also investigated。 The experimental results suggested that TiO2 NPs were accumulated in the mice testis by the blood testicular barrier, causing testis damaged, cell apoptosis, such as rare sperm, sperm breakages, rarefaction of testis cell, decreased germinative layer thickness, and irregular arrangement of testis cells of the seminiferous tubules etc。 Sperm was severely damaged in the cauda epididymis, sperm malformation rate increased, the fertility of male mice significantly decreased etc。 TiO2 NPs significantly increased ROS production, decreased SOD, GSH-PX, GST activities and GSH content, promoted peroxidation of lipids, proteins and DNA, downregulated Nrf2 and its target gene products including HO-1,GCLC, NQO1, PKC and PI3K expression, and upregulated Keap1 expression。 It implied that TiO2 NPs exposure contributes to the testicular damage in male mice and may involve Nrf2 signal pathway disordered。

Key words: Nano-sized TiO2; Mice; Testis; Oxidative stress; Nrf2 signaling pathway

第一部分研究背景 1

1 纳米氧化钛的特性及应用 1

2 纳米氧化钛颗粒进入小鼠睾丸的途径 1

2。1 鼻腔摄入 1

2。2 皮肤吸收 1

2。3 胃肠道吸收 2

3 纳米氧化钛的生物学毒性 2

3。1 对肺的毒性作用 2

3。2 对肝的毒性作用 3

3。3 对肾的毒性作用 3

3。4 对脑的毒性作用 4

3。5 生殖毒性 4

4 纳米氧化钛生殖毒性研究展望 4

5 研究思路 5

6 研究内容 5

7 论文创新点 5

第二部分源C于H优J尔W论R文M网WwW.youeRw.com 原文+QQ752-018766 纳米氧化钛致小鼠睾丸氧化损伤涉及Nrf2信号通路的功能紊乱纳米氧化钛致小鼠睾丸氧化损伤涉及Nrf2信号通路的功能紊乱:http://www.youerw.com/shengwu/lunwen_202963.html