本文選題：氟 + 兒童智力水平��； 參考：《華中科技大學(xué)》2012年碩士論文

【摘要】：氟在環(huán)境中廣泛存在，人體的暴露途徑主要是通過接觸食物、水及含氟的牙膏等產(chǎn)品。另外，工業(yè)污染和燃煤污染也已成為中國地區(qū)氟暴露的主要來源。長期攝入過量氟可引起嚴(yán)重的公共衛(wèi)生問題即氟中毒（fluorosis）。氟中毒在全球均有發(fā)生，且影響達(dá)數(shù)百萬人。氟除對牙齒和骨骼產(chǎn)生毒性效應(yīng)外，還具有神經(jīng)毒性。Roholm等發(fā)現(xiàn)氟對小鼠中樞神經(jīng)系統(tǒng)具有毒性作用，使其脊髓神經(jīng)纖維和小腦的外顆粒層細(xì)胞顯著減少，神經(jīng)元凋亡明顯增加。而且，氟可導(dǎo)致胎鼠神經(jīng)元密度和未分化神經(jīng)元數(shù)目發(fā)生改變。有研究報道，氟對大鼠行為產(chǎn)生不良效應(yīng)的嚴(yán)重程度與血清及大腦特定區(qū)域中氟離子濃度直接相關(guān)。人群流行病學(xué)調(diào)查表明，生活在氟中毒地區(qū)兒童的學(xué)習(xí)記憶能力和智力水平明顯低于生活在正常地區(qū)的兒童。 某一地區(qū)飲水中氟含量在一定時間內(nèi)是長期不變的。氟一旦被吸收進(jìn)入血液，容易分布全身。在兒童，大約80-90%氟被保留在體內(nèi)，其余主要經(jīng)腎臟排出體外，即氟在24h內(nèi)由尿排出攝氟量的50-92%。故血清氟濃度和尿氟濃度在一定程度上可作為人體內(nèi)氟蓄積水平的參考指標(biāo)。本次調(diào)查中，我們利用中國農(nóng)村聯(lián)合瑞文測驗(yàn)（CRT-RC）測試兒童智力水平（IQ），氟離子選擇電極法測定飲用水、兒童血清和尿液中氟濃度，并探討血清氟和尿氟濃度與兒童IQ之間的關(guān)系。 額葉前皮質(zhì)的多巴胺能調(diào)節(jié)個體的認(rèn)知過程、學(xué)習(xí)記憶能力和控制執(zhí)行能力。兒茶酚氧甲基移位酶（COMT）是影響多巴胺能神經(jīng)遞質(zhì)代謝的關(guān)鍵酶，可調(diào)節(jié)額葉前皮質(zhì)內(nèi)至少60%的多巴胺的降解。故個體COMT的活性變化可影響機(jī)體多巴胺的代謝過程，從而影響個體的認(rèn)知、學(xué)習(xí)過程。COMT基因在第158個密碼子存在一個G/A突變，使其編碼的氨基酸由纈氨酸（val）變成蛋氨酸（met），同時該酶也變成不耐熱的低活性形式。Egan等研究發(fā)現(xiàn)COMT基因多態(tài)性與兒童認(rèn)知能力之間具有相關(guān)性，但COMT基因多態(tài)性與氟中毒地區(qū)兒童認(rèn)知能力的關(guān)系目前尚未見報道。 有研究顯示，甲狀腺激素水平可作為檢測兒童智力低下的敏感指標(biāo)。蛋白質(zhì)作為生命功能的直接執(zhí)行者，它比基因更能直接的反映生理過程及其變化。因此，我們利用蛋白質(zhì)組學(xué)方法研究氟中毒發(fā)生發(fā)展過程中某些蛋白或多肽水平的變化，尋找差異表達(dá)蛋白，為尋找氟中毒兒童早期生物標(biāo)志物提供一定依據(jù)。 第一部分飲水高氟對兒童智力的影響 目的：探討高氟地區(qū)兒童血清氟、尿氟和甲狀腺激素水平與兒童智力水平的關(guān)系。 方法：收集兒童飲用水樣、尿樣和血液樣本。利用氟離子選擇電極法，放射免疫檢測試劑盒和中國農(nóng)村聯(lián)合版瑞文測試（CRT-RC）測定飲水氟、兒童尿氟及血清氟濃度、血清甲狀腺激素及兒童智力水平。 結(jié)果：高氟組和對照組兒童之間的飲水氟、尿氟、血清氟濃度、血清TSH水平和IQ得分均存在顯著性差異（P 0.05）。Spearman分析顯示尿氟、血清氟濃度與兒童IQ得分之間存在負(fù)相關(guān)關(guān)系（rs=-0.206, P 0.01; rs=-0.187, P 0.05）。 結(jié)論：長期攝入過量氟可影響兒童智力水平。 第二部分COMT基因多態(tài)性與兒童智力的關(guān)系 目的：探討COMTval158met多態(tài)性與兒童智力水平的關(guān)系。 方法：利用限制性片段長度多態(tài)性聚合酶鏈反應(yīng)（PCR-RFLP）辨別COMT基因多態(tài)性與兒童智力水平之間的關(guān)系。 結(jié)果：攜帶val/val基因型兒童的IQ得分明顯高于攜帶met/val、met/met基因型兒童的水平（P 0.001）。 結(jié)論：val/val的基因型表達(dá)可能對兒童的智力發(fā)展有保護(hù)作用。 第三部分高氟暴露兒童血漿蛋白組學(xué)研究 目的：檢測高氟暴露兒童血漿蛋白表達(dá)譜的改變以及相關(guān)蛋白的鑒定。 方法：高氟組10名兒童，對照組10名兒童。利用2-DE和Autoflex speed MALDI-TOF-TOF技術(shù)對兩組兒童血漿蛋白進(jìn)行分離鑒定。 結(jié)果：與對照組相比，在高氟組發(fā)現(xiàn)7個表達(dá)不同的蛋白點(diǎn)，經(jīng)質(zhì)譜共鑒定出5種表達(dá)上調(diào)的蛋白，，包括補(bǔ)體CIs亞單位前體、α-1-B糖蛋白、血紅素結(jié)合蛋白、載脂蛋白E前體以及免疫球蛋白輕鏈變異區(qū)域。 結(jié)論：氟中毒兒童血漿蛋白表達(dá)譜發(fā)生改變，為尋找氟中毒兒童的早期生物標(biāo)志物提供了一定基礎(chǔ)。
[Abstract]:In addition , industrial pollution and coal pollution have become the main source of fluoride exposure in China . In addition , industrial pollution and coal pollution have become the main source of fluoride exposure in China .

In this study , the concentration of fluorine and fluoride in drinking water , serum and urine of children were measured by using Chinese rural joint Swedish test ( CRT - RC ) , and the relationship between serum fluorine and urine fluoride concentration and IQ was discussed .

There is a G / A mutation at codon 158 of the COMT gene , which can affect the cognitive and learning process of the individual . The COMT gene has a correlation between the polymorphism of COMT gene and the cognitive ability of children .

It is shown that thyroid hormone level can be used as a sensitive index to detect children ' s mental retardation . Protein as the direct executor of the function of life reflects the physiological process and its changes more directly than the gene . Therefore , we study the changes of some proteins or polypeptide levels in the course of development of fluorosis by using the proteomic method , find out the differential expression protein , and provide some basis for finding the early biomarkers of fluorosis children .

The Effect of Drinking High Fluorine on the Intelligence of Children in Part I

Objective : To investigate the relationship between serum fluorine , urinary fluoride and thyroid hormone levels in children with high fluorine content and children ' s intelligence level .

Methods : Children ' s drinking water samples , urine samples and blood samples were collected . Use of fluoride ion selective electrode method , radioimmunoassay kit and Chinese rural joint version of Swedish test ( CRT - RC ) were used to determine the levels of fluoride in drinking water , urine fluoride of children and serum fluorine concentration , serum thyroid hormones and children ' s intelligence .

Results : The levels of fluoride , fluoride , serum fluorine , serum TSH and IQ scores between high fluoride group and control group were significantly different ( P 0.05 ) . The results showed that there was a negative correlation between urinary fluoride , serum fluorine concentration and IQ scores in children ( rs = - 0.206 , P 0.01 ; rs = - 0.187 , P 0.05 ) .

Conclusion : Long - term intake of excess fluoride can affect children ' s intelligence level .

The Relationship between the Polymorphism of the Second Part COMT Gene and the Intelligence of Children

Objective : To investigate the relationship between the polymorphism of COMTval158 met and the level of intelligence of children .

Methods : Using restriction fragment length polymorphism polymerase chain reaction ( PCR - RFLP ) to identify the relationship between COMT gene polymorphism and intelligence level of children .

Results : The IQ scores of children with val / val genotype were significantly higher than those with met / val and met / met genotypes ( P 0.001 ) .

Conclusion : The genotype expression of val / val may play a protective role in the intelligence development of children .

Study on Plasma Proteomics of the Third Part of High Fluorine Exposure Children

Objective : To detect the changes of plasma protein expression profile and the identification of related proteins in children exposed to high fluorine exposure .

Methods : 10 children in high fluorine group and 10 children in control group were separated and identified by 2 - DE and Autoflex speed MALDI - TOF - TOF technique .

Results : Compared with the control group , 7 expressed different protein spots were found in the high fluoride group . Five of the up - regulated proteins were identified by mass spectrometry , including complement , subunit precursor , 偽 - 1 - B glycoprotein , heme binding protein , apolipoprotein E precursor and immunoglobulin light chain variable region .

Conclusion : The expression profile of plasma protein in children with fluorosis is changed , which provides a basis for finding the early biomarkers of fluorosis children .
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R599.1

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本文編號：1998284