本文關(guān)鍵詞： 亞慢性砷暴露 微量元素 腦 性別　出處：《大連醫(yī)科大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景：砷（Arsenic，，As）是一種廣泛分布于土壤、巖石和水環(huán)境中的有毒類金屬元素。As在自然界中主要以化合物的形式存在，對(duì)健康具有多方面的危害，可以引發(fā)多器官和多系統(tǒng)的形態(tài)學(xué)和功能上的異常改變。As對(duì)神經(jīng)系統(tǒng)的影響主要表現(xiàn)為頭痛、嗜睡、煩躁、記憶力減退、定向力障礙，驚厥甚至昏迷等亞臨床的神經(jīng)損傷。人群流行病學(xué)調(diào)查和動(dòng)物實(shí)驗(yàn)研究均表明，As具有神經(jīng)毒性。慢性As暴露可導(dǎo)致腦組織損傷和病理形態(tài)學(xué)改變，但其毒作用機(jī)制尚不清楚。必需微量元素是維持機(jī)體生命活動(dòng)所必必需的物質(zhì)，具有多種重要的生理功能。在酶的活化、激素及維生素的合成與轉(zhuǎn)化、電子傳遞、調(diào)控自由基水平以及抗氧化等方面發(fā)揮著極為重要的作用。其中鐵（Fe）、鋅（Zn）、硒（Se）等必需微量元素與腦的發(fā)育和功能維持關(guān)系十分密切。一些流行病學(xué)調(diào)查和實(shí)驗(yàn)研究表明，As暴露能導(dǎo)致人和動(dòng)物血中多種必需微量元素濃度發(fā)生改變，提示As影響體內(nèi)必需微量元素濃度。然而，As暴露對(duì)腦組織必需微量元素濃度影響報(bào)道很少。本研究通過(guò)亞慢性染As小鼠60天，檢測(cè)As暴露小鼠腦組織中砷的濃度以及五種必需微量元素Fe、銅（Cu）、Zn、Se和鉻（Cr）的濃度，并探討這些必需微量元素在中樞神經(jīng)系統(tǒng)的濃度變化與As的神經(jīng)系統(tǒng)毒作用之間的內(nèi)在聯(lián)系。 目的：觀察As在小鼠大、小腦組織中蓄積程度，研究As對(duì)小鼠腦組織中主要必需微量元素Fe、Cu、Zn、Se、Cr濃度的影響，為探討砷的中樞神經(jīng)系統(tǒng)毒作用機(jī)制提供動(dòng)物實(shí)驗(yàn)依據(jù)。 方法：SPF級(jí)小鼠80只，按體重將小鼠隨機(jī)分為飲用水對(duì)照組、1ppmAs2O3染砷組、2ppmAs2O3染砷組、4ppmAs2O3染砷組。每組小鼠雌雄各半。通過(guò)自然飲用含不同濃度As2O3蒸餾水的方式使小鼠染砷，連續(xù)染毒60天后取腦組織。用電感耦合等離子體質(zhì)譜（Agilent7500ce ICP-MS）技術(shù)檢測(cè)小鼠腦組織As和Cu、Fe、Zn、Se和Cr的濃度差異。采用SPSS13.0統(tǒng)計(jì)軟件，用單因素方差分析（one-wayANOVA），比較各染砷組與對(duì)照組間的統(tǒng)計(jì)學(xué)差異，兩組間比較用Scheffe’s法分析，用多因素方差分析（two-wayANOVA）比較性別方面的差異。采用SPSS13.0軟件包對(duì)所有數(shù)據(jù)進(jìn)行整理和分析，以p0.05表示統(tǒng)計(jì)學(xué)差異顯著。 結(jié)果：在本次實(shí)驗(yàn)研究中，與對(duì)照組相比，亞慢性砷暴露1、2和4mg/L三氧化二砷（As2O3）染砷組小鼠全腦組織以及大腦和小腦組織中As濃度顯著高于對(duì)照組（p0.05），并隨染毒劑量增加而升高，呈現(xiàn)劑量-反應(yīng)關(guān)系。砷暴露小鼠大腦和小腦組織中Fe，Se和Cr的濃度顯著低于對(duì)照組（p0.05）。相反，砷暴露小鼠大腦和小腦組織中Cu的濃度顯著高于對(duì)照組（p0.05）。砷暴露對(duì)小鼠全腦組織中Cu和Se濃度的影響在性別間存在差異（p0.05），然而在砷暴露大腦組織中僅有Se濃度的變化在性別間統(tǒng)計(jì)學(xué)差異有意義（p0.05），但在小腦組織中As對(duì)Cu和Se濃度影響在性別間的差異與全腦組織中相同。 結(jié)論：亞慢性砷暴露小鼠大腦和小腦組織中As濃度顯著升高，這表明As暴露小鼠腦組織中存在As的蓄積。亞慢性砷暴露可能降低小鼠大腦和小腦組織中Fe，Se和Cr的濃度和升高小鼠大腦和小腦組織中Cu的濃度。此外，砷暴露對(duì)小鼠大腦組織中的Se濃度和小腦組織中Cu和Se濃度的影響存在性別差異。因此，需要更多的實(shí)驗(yàn)進(jìn)一步證明，As誘導(dǎo)的中樞神經(jīng)系統(tǒng)損害是否與微量元素水平的變化密切相關(guān)。同時(shí)，As對(duì)腦組織中必需微量元素濃度的影響和誘導(dǎo)的性別差異的機(jī)制仍需要進(jìn)一步的探討。
[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.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R114

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