亚慢性砷暴露对小鼠脑组织多种必需微量元素浓度的影响

发布时间：2018-03-02 00:32

本文关键词： 亚慢性砷暴露微量元素脑性别　出处：《大连医科大学》2013年硕士论文　论文类型：学位论文

【摘要】：研究背景：砷（Arsenic，，As）是一种广泛分布于土壤、岩石和水环境中的有毒类金属元素。As在自然界中主要以化合物的形式存在，对健康具有多方面的危害，可以引发多器官和多系统的形态学和功能上的异常改变。As对神经系统的影响主要表现为头痛、嗜睡、烦躁、记忆力减退、定向力障碍，惊厥甚至昏迷等亚临床的神经损伤。人群流行病学调查和动物实验研究均表明，As具有神经毒性。慢性As暴露可导致脑组织损伤和病理形态学改变，但其毒作用机制尚不清楚。必需微量元素是维持机体生命活动所必必需的物质，具有多种重要的生理功能。在酶的活化、激素及维生素的合成与转化、电子传递、调控自由基水平以及抗氧化等方面发挥着极为重要的作用。其中铁（Fe）、锌（Zn）、硒（Se）等必需微量元素与脑的发育和功能维持关系十分密切。一些流行病学调查和实验研究表明，As暴露能导致人和动物血中多种必需微量元素浓度发生改变，提示As影响体内必需微量元素浓度。然而，As暴露对脑组织必需微量元素浓度影响报道很少。本研究通过亚慢性染As小鼠60天，检测As暴露小鼠脑组织中砷的浓度以及五种必需微量元素Fe、铜（Cu）、Zn、Se和铬（Cr）的浓度，并探讨这些必需微量元素在中枢神经系统的浓度变化与As的神经系统毒作用之间的内在联系。目的：观察As在小鼠大、小脑组织中蓄积程度，研究As对小鼠脑组织中主要必需微量元素Fe、Cu、Zn、Se、Cr浓度的影响，为探讨砷的中枢神经系统毒作用机制提供动物实验依据。方法：SPF级小鼠80只，按体重将小鼠随机分为饮用水对照组、1ppmAs2O3染砷组、2ppmAs2O3染砷组、4ppmAs2O3染砷组。每组小鼠雌雄各半。通过自然饮用含不同浓度As2O3蒸馏水的方式使小鼠染砷，连续染毒60天后取脑组织。用电感耦合等离子体质谱（Agilent7500ce ICP-MS）技术检测小鼠脑组织As和Cu、Fe、Zn、Se和Cr的浓度差异。采用SPSS13.0统计软件，用单因素方差分析（one-wayANOVA），比较各染砷组与对照组间的统计学差异，两组间比较用Scheffe’s法分析，用多因素方差分析（two-wayANOVA）比较性别方面的差异。采用SPSS13.0软件包对所有数据进行整理和分析，以p0.05表示统计学差异显著。结果：在本次实验研究中，与对照组相比，亚慢性砷暴露1、2和4mg/L三氧化二砷（As2O3）染砷组小鼠全脑组织以及大脑和小脑组织中As浓度显著高于对照组（p0.05），并随染毒剂量增加而升高，呈现剂量-反应关系。砷暴露小鼠大脑和小脑组织中Fe，Se和Cr的浓度显著低于对照组（p0.05）。相反，砷暴露小鼠大脑和小脑组织中Cu的浓度显著高于对照组（p0.05）。砷暴露对小鼠全脑组织中Cu和Se浓度的影响在性别间存在差异（p0.05），然而在砷暴露大脑组织中仅有Se浓度的变化在性别间统计学差异有意义（p0.05），但在小脑组织中As对Cu和Se浓度影响在性别间的差异与全脑组织中相同。结论：亚慢性砷暴露小鼠大脑和小脑组织中As浓度显著升高，这表明As暴露小鼠脑组织中存在As的蓄积。亚慢性砷暴露可能降低小鼠大脑和小脑组织中Fe，Se和Cr的浓度和升高小鼠大脑和小脑组织中Cu的浓度。此外，砷暴露对小鼠大脑组织中的Se浓度和小脑组织中Cu和Se浓度的影响存在性别差异。因此，需要更多的实验进一步证明，As诱导的中枢神经系统损害是否与微量元素水平的变化密切相关。同时，As对脑组织中必需微量元素浓度的影响和诱导的性别差异的机制仍需要进一步的探讨。
[Abstract]:Background: arsenic (Arsenic, As) is a widely distributed in soil, toxic metal elements of rock and water environment in.As in nature mainly in the compound form, has great harm to health, can cause the morphological and function multi organ and multi system to the abnormal change of.As effect the nervous system mainly manifested as headache, drowsiness, irritability, memory loss, disorientation, seizures and even coma subclinical neurological damage. Epidemiological investigations and animal experiments research showed that As have neurotoxicity. Chronic As exposure can cause brain damage and pathological changes, but the mechanism of toxicity is still not clear. The essential trace element is to maintain the life activities of the human body have the necessary material, has many important physiological functions. In enzyme activation, synthesis and transformation, hormones and vitamins electron transfer, transfer Control the level of free radical and antioxidant plays a very important role. The iron (Fe), zinc (Zn), selenium (Se) and other essential trace elements and the development of brain function and maintain very close relationship. Some epidemiological and experimental studies indicate that As exposure can lead to the change of essential trace element concentrations a variety of human and animal blood, suggesting that As effects of in vivo essential trace element concentration. However, As exposure on brain tissue effects of essential trace elements were rarely reported. The study by subchronic exposure to As mice for 60 days, the detection of As concentration in the brain of mice exposed to arsenic and five essential trace elements Fe, Cu (Cu) Zn, Se, and Cr (Cr) concentration, and to explore the relationship between these essential trace elements in the concentration and As of the central nervous system nervous system toxicity.
Objective: To observe the accumulation degree of As in the large cerebellar tissue of mice, and to study the effect of As on the concentrations of Fe, Cu, Zn, Se and Cr in the brain tissue of mice, and to provide animal experimental evidence for exploring the toxic mechanism of arsenic in the central nervous system.
Methods: SPF 80 mice, the mice were randomly divided into control group according to the weight of drinking water, arsenic 1ppmAs2O3 group, 2ppmAs2O3 4ppmAs2O3 group exposed to arsenic, arsenic groups. Each group were female. Through natural drinking water containing As2O3 of distilled water with different concentrations of the mice exposed to arsenic, after 60 days from brain tissue. By inductively coupled plasma mass spectrometry (Agilent7500ce ICP-MS) were detected in brain tissue of As and Cu, Fe, Zn, Se and Cr concentration difference. Using SPSS13.0 statistical software, using single factor variance analysis (one-wayANOVA), compare the difference of arsenic exposed group and control group, the two groups using Scheffe s analysis of variance analysis, multiple factors (two-wayANOVA) differences in gender. Of all the data were collected and analyzed by SPSS13.0 software, P0.05 statistically significant difference.
Results: in this study, compared with the control group, 1,2 and 4mg/L of arsenic trioxide (As2O3) exposed to arsenic arsenic groups and whole brain tissue of mice brain and cerebellum As concentration was significantly higher than the control group (P0.05), and with the dose increased, showing a dose-response relationship and the brain. Cerebellar tissue Fe in mice exposed to arsenic concentration, Se and Cr were significantly lower than the control group (P0.05). On the contrary, arsenic concentration in cerebral cortex and cerebellar tissue of mice in Cu was significantly higher than the control group (P0.05). Arsenic exposure effects on Cu and Se concentration in brain tissue in mice in the gender differences between (P0.05) however, only the concentration of Se in arsenic exposed changes of brain tissues in sex between statistically significant (P0.05), but the difference in the effect of As on cerebellum Cu and Se concentration in gender and in the whole brain.
Conclusion: the concentration of As in brain and cerebellum of mice increased significantly in chronic arsenic exposure, suggesting that As exposure to As accumulation was found in the brain of mice. May reduce cerebral and cerebellar tissue of mice in Fe exposure to arsenic concentration, the concentration of Se and Cr and increase of mouse brain and cerebellum in Cu. In addition, arsenic exposure to sex differences in the effects of Cu and Se concentration in brain tissue in mice and the concentration of Se in cerebellum. Therefore, the need for more experiments further prove that the central nervous system damage induced by As and whether changes in the levels of trace elements are closely related. At the same time, the mechanism of As on gender differences in the brain effects of essential trace element concentrations the induction and still need further discussion.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R114

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