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Endocrine disrupting effect of Di - (2 - ethylhexyl) phthalate on rats and proteome analysis of their pituitary and hypothalamus

邻苯二甲酸二(2-乙基己基)酯对大鼠的内分泌干扰作用及其垂体和下丘脑蛋白质组分析

基本信息

批准号：
16510042
负责人：
SAKAMOTO Yasushi
金额：
$ 1.41万
依托单位：
SAITAMA MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer and is a ubiquitous environmental contaminant which may have adverse effects on human reproductive health. Additionally, no binding ability of DEHP to sex hormone receptors already reported. Therefore, a mode of action affecting an endocrine function of a living body is not clarified.In this examination, we investigated about the affection of DEHP to fetus and infant of rat. Pregnant and lactation rats are used in this working the effect of DEHP to the fetus and infant, respectively and carried out proteome-based analyses of the endocrine organs of these child rats.Control group, pregnant group and lactation group of F344 rats are prepared. In control group, only administrations of sesame oil were carried out. In pregnant group, 15 times of administrations of DEHP were performed with a dose of the 0.5g/kg/day from after 2 days of pregnancy. In lactation group, 17 times of administrations are done with the same dosage from 2^<nd> day a … More fter delivery. After the each administration period, child rats were separated form mother rats and were bred for 4 month in no administration, and then endocrine organs of them were eviscerated.No significant body weights were found between the treated or control group but pituitaries weight were significantly increased in child rats of pregnant and lactation group (p > 0.05). Thus the indirect intake of DEHP seemed to be affective on pituitary of child rats, therefore, protein difference analyses with two-dimensional electrophoresis were performed on the pituitary in the three groups. Four interest protein spots were found and proteome based analyses for these proteins were performed. As a result, these proteins were identified to be somatotropin receptor, adenine phosphoribosyltransferase, proteaseme activator complex subunit1 and prohibin through the study of the database search with MSCOT (http://www.matrixscience.com). These proteins seems to be reflecting the effect of DEHP to living body and to be important for elucidating the endocrine disrupting effect mechanism of DEHP. Less

邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种增塑剂，是一种普遍存在的环境污染物，可能对人类生殖健康产生不利影响。此外，DEHP与性激素受体的结合能力也未见报道。因此，影响活体内分泌功能的作用模式尚不明确。本实验探讨了DEHP对大鼠胎仔的影响。本研究采用妊娠大鼠和哺乳期大鼠分别研究DEHP对胎儿和幼鼠的影响，并对这些幼鼠的内分泌器官进行了蛋白质组学分析。制备F344大鼠对照组、妊娠组和哺乳期组。对照组只给予香油治疗。妊娠组从妊娠第2天开始，以0.5g/kg/天的剂量给药DEHP 15次。哺乳期组在分娩后1 ~ 2天，以相同剂量共给药17次。每个给药期结束后，将仔鼠与母鼠分离，在不给药的情况下饲养4个月，然后去脏器。妊娠和哺乳期组大鼠垂体重量显著增加（p < 0.05），对照组大鼠体重差异无统计学意义（p < 0.05）。由此可见，间接摄入DEHP可能对儿童大鼠垂体有影响，因此，我们对三组大鼠垂体进行了双向电泳蛋白差异分析。发现了四个感兴趣的蛋白点，并对这些蛋白进行了基于蛋白质组学的分析。通过MSCOT数据库检索（http://www.matrixscience.com）的研究，鉴定出这些蛋白分别为生长激素受体、腺嘌呤磷酸核糖基转移酶、蛋白酶素激活物复合物亚单位1和禁止蛋白。这些蛋白可能反映了DEHP对生物体的影响，对阐明DEHP的内分泌干扰作用机制具有重要意义。少