本文關(guān)鍵詞： BDE-209 窒息 神經(jīng)行為學(xué)表現(xiàn) capase-3 mTOR　出處：《廣州醫(yī)科大學(xué)》2014年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：研究背景: 因其具有良好的阻燃性能和尚未明確的毒理學(xué)機(jī)制，，十溴聯(lián)苯醚(Decabrominated diphenyl ether，BDE-209)被廣泛應(yīng)用于電路板、紡織品、塑料制品和建筑相關(guān)材料中[1]。研究表明，BDE-209在使用和生產(chǎn)過(guò)程中可經(jīng)滲出、揮發(fā)等方式釋放到周?chē)h(huán)境中，并通過(guò)食物鏈最終在人體內(nèi)蓄積。中國(guó)是世界上使用及生產(chǎn)BDE-209最多的國(guó)家。目前越來(lái)越多的研究顯示BDE-209是近年我國(guó)環(huán)境中含量增長(zhǎng)較快的持久性環(huán)境有機(jī)污染物，平均每天人體經(jīng)呼吸攝入416ngBDE-209[2]，人體血清、乳汁及臍血中BDE-209平均濃度分別為9.472ng/gliquid weight，1.867ng/g liquid weight和78.103ng/g liquid weigh[3]。因?yàn)轶w內(nèi)蓄積的差異性、解毒代謝和排除機(jī)制的不完善，處于生長(zhǎng)發(fā)育時(shí)期的嬰幼兒體內(nèi)BDE-209的暴露水平遠(yuǎn)高于成年水平[4]。此外，胚胎及嬰幼兒時(shí)期是腦神經(jīng)發(fā)育和功能完善的關(guān)鍵時(shí)期，對(duì)外源性毒物的損傷尤為敏感。因此，BDE-209對(duì)神經(jīng)系統(tǒng)發(fā)育的影響備受關(guān)注。 圍產(chǎn)期窒息是導(dǎo)致神經(jīng)發(fā)育異常的主要原因之一。據(jù)統(tǒng)計(jì)，70-80%的神經(jīng)發(fā)育異常是由圍產(chǎn)期窒息所致。隨著醫(yī)療水平的提高，圍產(chǎn)期窒息發(fā)生率已明顯減低，但因?qū)е律窠?jīng)系統(tǒng)發(fā)育異常原因眾多，后者的發(fā)生率并未降低，約為為1/1000。環(huán)境化學(xué)因素是眾多造成神經(jīng)發(fā)育異常的因素中備受關(guān)注的一種。此外，日益增多的證據(jù)表明，圍產(chǎn)期窒息可增加已受環(huán)境因素影響的胎兒發(fā)生神經(jīng)發(fā)育異常的風(fēng)險(xiǎn)[18]。目前，我國(guó)有關(guān)神經(jīng)發(fā)育異常環(huán)境因素的研究較少，其對(duì)妊娠結(jié)局影響的研究亦不多。因此，在我國(guó)的環(huán)境污染控制工作匱乏,當(dāng)今環(huán)境污染日益增加的形勢(shì)下，探討環(huán)境因素與圍產(chǎn)期窒息對(duì)神經(jīng)系統(tǒng)發(fā)育異常影響的聯(lián)合作用有著重要的社會(huì)和經(jīng)濟(jì)意義。 研究目的: 建立BDE-209圍產(chǎn)期單獨(dú)暴露或聯(lián)合產(chǎn)時(shí)窒息的SD大鼠的子鼠模型。根據(jù)子鼠的生長(zhǎng)發(fā)育及神經(jīng)反射指標(biāo)，海馬組織中凋亡相關(guān)基因如caspase-3,mTOR的表達(dá)，在MORRIS水迷宮中的學(xué)習(xí)及記憶能力，初步探討B(tài)DE-209或聯(lián)合產(chǎn)時(shí)窒息對(duì)子鼠生長(zhǎng)和神經(jīng)發(fā)育可能造成的影響，為BDE-209的毒理學(xué)研究及窒息的神經(jīng)損害作用提供理論依據(jù)。 研究方法: 1.BDE-203圍產(chǎn)期暴露 自孕鼠受孕第一天開(kāi)始，根據(jù)分組每日分別胃灌0mg/Kg（對(duì)照組）,0.6mg/Kg,6.0mg/KgBDE209。 2.產(chǎn)時(shí)窒息模型 孕鼠于妊娠22天接受剖宮產(chǎn)手術(shù)，含有子鼠的雙側(cè)子宮被完整取出，根據(jù)分組立即娩出（非窒息組）或置于37℃水浴箱15分鐘后娩出（窒息組），子鼠由代育母鼠哺育。 3.BDE209暴露聯(lián)合窒息對(duì)子鼠生理發(fā)育的影響 自出生后第一天至出生后第33天，每日檢查子鼠張耳、全身絨毛、下牙萌出、開(kāi)眼、上牙萌出、全身絨毛等生理發(fā)育指標(biāo)。 4. BDE209暴露聯(lián)合窒息對(duì)子鼠行為學(xué)的影響 自出生后第一天至出生后第33天，每日檢查子鼠痛覺(jué)反射、平面翻正、負(fù)趨地性、懸崖回避、聽(tīng)覺(jué)驚厥、空中翻正等神經(jīng)反射指標(biāo)和前肢懸掛試驗(yàn)等耐力試驗(yàn)。 5. BDE209暴露聯(lián)合窒息對(duì)子鼠學(xué)習(xí)記憶的影響 通過(guò)MORRIS水迷宮測(cè)試出生后第二十八天的雄性子鼠的學(xué)習(xí)記憶能力。 6. BDE209暴露聯(lián)合窒息對(duì)子鼠海馬組織中caspase3及mTOR基因表達(dá)的影響 通過(guò)RT-PCR檢測(cè)產(chǎn)出生后第6日雄性子鼠雙側(cè)海馬組織中caspase-3基因及mTOR基因的表達(dá)。 7.統(tǒng)計(jì)學(xué)分析 應(yīng)用SPSS18.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析，數(shù)據(jù)結(jié)果以±s表示，行方差齊性檢驗(yàn)和卡方檢驗(yàn)，檢驗(yàn)水準(zhǔn)為α＝0.05。P0.05為差異有統(tǒng)計(jì)學(xué)意義。 結(jié)果: 1.各組子鼠的痛覺(jué)反射、聽(tīng)覺(jué)驚厥、空中翻正等神經(jīng)反射指標(biāo)達(dá)標(biāo)日齡的差異，無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）。窒息組較非窒息組的子鼠，在平面翻正、負(fù)趨地性、懸崖回避達(dá)標(biāo)日齡的差異有統(tǒng)計(jì)學(xué)意義（P0.05），窒息組或非窒息組內(nèi)，不同劑量BDE-209暴露的子鼠間的各神經(jīng)反射指標(biāo)無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）。 2.與對(duì)照組相比，0.6mg/KgBDE-209暴露聯(lián)合產(chǎn)時(shí)窒息組雄性子鼠的上肢懸掛時(shí)間的差異有統(tǒng)計(jì)學(xué)意義（P0.05）。 3.各組子鼠的張耳、全身絨毛、下牙萌出、開(kāi)眼、上牙萌出、全身絨毛、陰道開(kāi)口、睪丸下降等生理發(fā)育指標(biāo)的差異沒(méi)有統(tǒng)計(jì)學(xué)意義（P0.05）。 4.各組雄性子鼠在MORRIS水迷宮中的定位航行試驗(yàn)所用的時(shí)間，空間探索試驗(yàn)中原平臺(tái)象限滯留時(shí)間占總時(shí)間的百分比的差異無(wú)統(tǒng)計(jì)學(xué)意義（P0.05） 5.各組子鼠雙側(cè)海馬中的caspase-3和mTOR基因表達(dá)，RT-PCR結(jié)果顯示，各組mTOR基因表達(dá)水平的差異無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）；與對(duì)照組相比，各組caspase-3的差異有統(tǒng)計(jì)學(xué)意義（P0.05），且與BDE-209暴露存在劑量關(guān)系。 結(jié)論: 圍產(chǎn)期BDE-209單獨(dú)暴露和或聯(lián)合窒息對(duì)子鼠可能存在一定的影響。
[Abstract]:Research background:
Because of its flame retardant properties and toxicological mechanism of good is not clear, ten polybrominated diphenyl ether (Decabrominated diphenyl, ether, BDE-209) is widely used in circuit boards, textiles, plastic products and related research of [1]. building materials show that BDE-209 production process by exudation in use and volatilization etc., released to the surrounding environment and through the food chain, eventually accumulate in the body. Chinese is used in the world and production of BDE-209 in most countries. Now more and more studies show that BDE-209 is the content of China's environment of persistent organic pollutants in the environment of rapid growth, the average daily intake of the body through the respiratory 416ngBDE-209[2], human serum, milk and umbilical blood in average BDE-209 the concentration were 9.472ng/gliquid weight, 1.867ng/g liquid weight and 78.103ng/g liquid weigh[3]. because of differences in the accumulation, metabolism and detoxification row The mechanism is not perfect, in the exposure period of growth and development of BDE-209 in infants is much higher than the level of [4]. in the embryonic and adult, the infant period is a critical period of brain neural development and function perfect, particularly sensitive to exogenous toxic injury. Therefore, BDE-209 has attracted much attention on the development of the nervous system.
Perinatal asphyxia is one of the main causes of abnormal neural development. According to statistics, 70-80% nerve dysplasia is caused by perinatal asphyxia. With the improvement of medical standards, perinatal asphyxia rate has decreased significantly, but due to nervous system abnormalities of many reasons, the latter did not reduce the incidence, about factors 1/1000. environmental chemistry is a concern due to many factors of abnormal neural development. In addition, the increasing evidence that perinatal asphyxia can increase the impact of environmental factors of fetal nerve dysplasia risk [18]. at present, our country related environmental factors of abnormal neural development is less, to study its effect on pregnancy the outcome is not much. Therefore, in China's environmental pollution control work is scarce, the environmental pollution is increasing under the situation of the environmental factors and perinatal asphyxia on The combination of the effects of the dysplasia of the nervous system has important social and economic significance.
The purpose of the study is:
Rat model of SD rats to establish BDE-209 perinatal asphyxia exposed alone or combined with intrapartum. According to the growth and development of offspring and nerve reflex index, hippocampus apoptosis related genes such as Caspase-3, the expression of mTOR, the ability of learning and memory in the MORRIS water maze, a preliminary study of BDE-209 or combined with birth asphyxia may influence the growth of rat offspring and neural development, and provide a theoretical basis for nerve damage toxicology and asphyxia BDE-209 role.
Research methods:
Perinatal exposure of 1.BDE-203
From the first day of pregnancy of pregnant rats, 0mg/Kg (control group), 0.6mg/Kg, 6.0mg/KgBDE209., respectively according to the group daily gastric perfusion (control group)
2. time asphyxiation model
On the 22 day of pregnancy of pregnant rats received cesarean section, containing the rat bilateral uterine was removed according to the packet delivered immediately (non asphyxia group) or under 37 DEG C water bath 15 minutes after childbirth (asphyxia group), rats by feeding. The surrogate mother
The effect of 3.BDE209 exposure and asphyxia on the physiological development of the rats
Since the first day of birth after thirty-third days, daily check at Zhang Er, body hair, teeth out of his eyes, teeth adorable, adorable, hair and other indicators of physiological development. The body
The effect of 4. BDE209 exposure combined with asphyxia on the behavior of children
Since the first day of birth after thirty-third days, the daily inspection of offspring pain reflex, surface righting reflex, negative geotaxis, cliff avoidance, auditory convulsion, air righting reflex and forelimb hanging test index and endurance test.
The effect of 5. BDE209 exposure combined with asphyxia on the learning and memory of the offspring
The ability of learning and memory of twenty-eighth days of male mice by MORRIS water maze test after birth.
Effects of 6. BDE209 exposure and asphyxia on the expression of Caspase3 and mTOR gene in the hippocampus of rat
The expression of Caspase-3 RT-PCR detected sixth days after the birth of bilateral hippocampus in male mice and mTOR gene.
7. statistical analysis
SPSS18.0 software was used for statistical analysis. The results of data were expressed in terms of + s, and the test of variance homogeneity and chi square test showed that the level of detection was 0.05.P0.05 = 1, the difference was statistically significant.
Result:
The 1. groups were pain reflex, auditory convulsion, air righting reflex and other indicators of the age difference, no statistical significance (P0.05). Group than in the non asphyxia group were asphyxia, is over the plane, negative geotaxis, cliff avoidance standard age difference was statistically significant (P0.05), asphyxia group or non asphyxia group, no statistical significance of each index reflex of different doses of BDE-209 exposed offspring between (P0.05).
2. compared with the control group, there was a significant difference in the upper limb suspension time between the 0.6mg/KgBDE-209 exposure group and the male asphyxia group (P0.05).
Ear, 3. groups offspring body hair, teeth and adorable, his eyes, teeth adorable, body hair, vaginal opening, testis physiological index of growth difference was not statistically significant (P0.05).
4., there was no significant difference in the time of location and voyage test of male rats in the MORRIS water maze, and the percentage of detention time in the central quadrant of the platform in the total time was not statistically significant (P0.05).
The expression of Caspase-3 and mTOR genes in 5. groups were bilateral hippocampus, RT-PCR results showed that the expression of mTOR mRNA level of the difference was not statistically significant (P0.05); compared with the control group, there was statistically significant difference between the groups of Caspase-3 (P0.05), and the exposure dose relationship with BDE-209.
Conclusion:
The perinatal BDE-209 exposure and or combined asphyxia may have a certain effect on the offspring.

【學(xué)位授予單位】：廣州醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R714.7

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