【作者】 杨丹；

【导师】 严云勤；

【作者基本信息】 东北农业大学 ， 发育生物学， 2008， 硕士

【摘要】 双酚A(Bisphenol A,BPA)广泛存在于塑料制品中,随着社会生产的迅猛发展,塑料制品的广泛应用,成为人们在生产生活中不可避免接触到的一类环境雌激素。BPA对机体的不良影响,已受到人们的广泛关注。BPA对机体的影响是多方面的,主要包括生殖系统、胚胎发育、神经系统、免疫系统、肿瘤发生等。BPA对雄性生殖系统的影响研究较多,大量动物实验证明,BPA几乎能够引起各种雄性生殖系统异常,对雄性生殖系统的发育和功能有较为广泛的影响。BPA对雌性生殖系统也有影响,BPA与卵巢囊肿、子宫内膜异位症、子宫肌瘤、子宫内膜癌等疾病的发生有密切的关系,并能诱发流产,降低生育率和妊娠率。但目前对BPA对雌性生殖系统影响的研究仍不全面,尤其对其复杂的作用机制的了解仍不够完善。因此,对BPA对小鼠子宫的影响及其分子机制的研究,能够为BPA诱导生殖系统疾病致病机制的研究提供一定的理论和实验依据,以期进一步加深人们对BPA的认识。同时也为BPA诱导肿瘤的预防、治疗及诊断提供依据。本实验主要采用子宫生长实验、RT-PCR,Western-blot及免疫组化等实验方法,研究了BPA处理后去势小鼠子宫湿重、脏器系数变化,ERa、phospho-ERα、ERβ、phospho-ERβ及凋亡基因Bcl-2/Bax在小鼠子宫中的分布及表达。实验结果表明:1)BPA具有雌激素样效应,可使去势小鼠子宫总体呈现增殖趋势,子宫肌层增厚,腺体增多,子宫腔增大等一系列形态学变化。2)BPA可使子宫内雌激素受体表达量增加,可激活ER,磷酸化受体表达量增加,其中子宫内膜、腺上皮ER表达变化明显,表明ER的合成及表达受BPA的调控, BPA的雌激素样效应可能通过ER途径起作用。3)BPA可明显上调Bcl-2基因的表达,并抑制Bax基因的表达,抑制细胞凋亡,促进细胞增殖,但在子宫内膜,腺上皮又上调Bax基因的表达,BPA诱导子宫增殖的同时可能对子宫内膜、腺上皮等功能性细胞有一定的损害。更多还原

【Abstract】 Bisphenol A(BPA) is a kind of environmental estrogens which broadly existed in plastic products and it can not be avoided touching in our lives as the development of social production and the wider useing of plastic products. More and more People already pay attention to the adverse effects of BPA. The effects of BPA impacting on organism have many aspects include reproductive system, embryonic development, nervous system, immune system, tumor genesis and so on. There are a lot of researches of BPA on the male reproductive system. Large number of animal experiments proved that BPA may almost cause all male reproductive system abnormalities including the functions and the developments. BPA also could affect the female reproductive system. BPA may related to ovarian cysts, endometriosis, uterine fibroids, endometrial cancer and so on. BPA may induce abortion, reducing fertility and pregnancy. But the study of BPA on the female reproductive system is not comprehensive, especially its complex understanding mechanism. Studying the effects of BPA impacting on mouse uterus and its molecular mechanism will provide the theoretical and experimental basis for the pathogenic mechanism of reproductive system diseases inducing by BPA, deeping people’s understanding of BPA. It also will provide the basis for BPA-induced tumor’s prevention, treatment and diagnosis.Using uterine growth experiment, we detected uterine wet weight and organ coefficient of ovariectomized mice treated by BPA. Using RT-PCR, Western-blot and immunohistochemistry methods, we detected gene changes of distribution and expression in the uterus of ovariectomized mice treated by BPA, including ERα, phospho-ERα, ERβ, phospho-ERβ, Bcl-2 and Bax. The results as showed:1) BPA has estrogen effects which can show the whole uterus in ovariectomized mice proliferation trends: myometrium thickening, glands increasing, uterine cavity increasing.2) BPA can cause changes of the expression of ER, so its estrogen-like effect may play a role through the ER channels.3) BPA caused apoptosis gene Bcl-2, Bax expression changes, induced endometrial and glandular epithelial cell apoptosis. BPA can induce proliferation in the uterus ,at the same time it may have some functional cell damage.更多还原