本文選題：雙酚A + 圍產期��； 參考：《華中科技大學》2012年碩士論文

【摘要】：目的：雙酚A（Bisphenol A, BPA）是一種典型的環(huán)境內分泌干擾物，主要應用于食品包裝行業(yè)和牙科，如用于生產聚碳酸酯和無數塑料制品，包括光盤，食品內襯，熱（傳真）紙，安全帽，粘合劑，粉末涂料等。它的廣泛使用，對環(huán)境造成了嚴重的污染，對人類的健康也造成了極大的威脅。已有研究顯示，在青春發(fā)育期，對SD雄性幼鼠進行BPA的亞急性暴露，可造成大鼠的腎臟損害，并可導致腎積水。但是圍產期ＢＰＡ暴露是否可導致子代大鼠腎臟的損害還不清楚。本研究采用了圍產期ＢＰＡ暴露的大鼠動物試驗模型，研究ＢＰＡ對子代大鼠腎臟損害的影響。方法：在整個妊娠期和泌乳期，懷孕的Wistar母鼠采用隨機的方法分為三組：對照組（玉米油）、低劑量組（50μg/kg/day BPA）、高劑量組（250μg/kg/day BPA）。三組大鼠分別接受各組別劑量的灌胃染毒，直至斷乳后，子代接受常規(guī)飲食至15周。監(jiān)測子代的體重以及其他生理指標的變化。于第15周時收集尿液、斷頭處死各組仔鼠，收集腎臟等主要臟器。用生化分析儀、ＨＥ染色、Masson染色、實時定量PCR、免疫印跡、免疫組織分析等技術分別檢測尿肌酐（creatinine，CR）、尿素氮(ureanitrogen, BUN)、尿蛋白（Urine protein, UPE）等生化指標、腎臟的病理學改變、腎積水纖維化相關分子TGF-β1、Smad2、VEGF、EGF、ET-1、CD40、CD3、Ⅳ型膠原蛋白等的mRNA的表達水平及蛋白水平的改變。 結果：哺乳期間，BPA暴露組子代體重與對照組相比，變化沒有差異。斷乳后，至第15周處死時，子代雌性大鼠的體重和腎重及腎臟系數與對照相比，差別未有統(tǒng)計學意義，而子代各劑量組雄鼠與對照組相比，體重增加，有統(tǒng)計學差異。第15周齡各劑量組子代雄鼠的腎重及腎臟系數與對照組相比，有減小趨勢，但未有統(tǒng)計學差異。各劑量組雌性大鼠的UPE、BUN、CR差異均無統(tǒng)計學意義，而雄性大鼠的UPE和CR與對照組相比顯著升高。而BUN與對照組比較無統(tǒng)計學差異。各組雄性大鼠的腎臟切片呈現一定的病理變化，包括腎實質變薄，腎間質增寬，腎小管擴張、腎小囊擴張，部分腎小球結構破壞，，失去正常形態(tài)，伴細胞浸潤。各劑量組雄性子代大鼠腎臟纖維化相關分子TGF-β1及其下游調控分子Smad2的ｍRNA表達增強，VEGF的ｍRNA表達顯著減弱。同時，免疫印跡結果也顯示，TGF-β1、Smad2、VEGF的蛋白表達量也有相應的變化趨勢。各劑量組EGF的ｍRNA表達量下降，但未有統(tǒng)計學差異。低劑量組ET-1ｍRNA表達量顯著升高，有統(tǒng)計學意義。免疫組化的結果顯示，劑量組腎間質CD3+T淋巴細胞較對照組增多，低劑量組腎小管上皮細胞CD40的表達也顯著增強。各劑量組IV型膠原在腎小管上皮細胞胞漿和基底膜呈陽性表達。結論：圍產期（50μg/kg/day、250μg/kg/day）BPA暴露可影響成年子代雄性大鼠的腎臟功能，其腎臟出現積水和纖維化樣改變。圍產期BPA暴露對子代雄性大鼠腎臟的影響存在劑量效應關系。
[Abstract]:Objective: bisphenol A bisphenol A (BPAA) is a typical environmental endocrine disruptor, mainly used in food packaging industry and dentistry, such as the production of polycarbonate and countless plastic products, including optical discs, food lining, hot (fax) paper, safety helmet, etc.Adhesives, powder coatings, etc.Its wide use has caused serious pollution to the environment and great threat to human health.Studies have shown that subacute exposure to BPA in young SD rats during puberty can cause kidney damage and hydronephrosis in rats.But it is unclear whether perinatal BPA exposure can lead to kidney damage in offspring.In this study, the effects of BPA on renal damage of offspring rats were studied by using the animal model of perinatal BPA exposure.Methods: during pregnancy and lactation, pregnant Wistar rats were randomly divided into three groups: control group (corn oil), low dose group (50 渭 g/kg/day) and high dose group (250 渭 g/kg/day).Three groups of rats were given intragastric administration of each group until weaning, and their offspring were fed a regular diet for 15 weeks.The body weight and other physiological indexes of the offspring were monitored.Urine was collected at week 15, rats were killed and kidney organs were collected.The biochemical indexes, such as urinary creatinine creatinine, urea nitrogen, bun, urinal protein, UPEN, and the pathological changes of kidney were detected by biochemical analyzer, real-time quantitative PCR, immunoblotting, immunohistochemistry and other techniques, such as ureanitrogen, ureanitrogen, urinal protein, UPEN, and so on.Changes of mRNA expression level and protein level of TGF- 尾 _ 1 Smad2 + VEGFT-1 CD40 CD40 CD3, 鈪

本文編號：1761386