双酚A与女童单纯乳房早发育及中枢性性早熟关系的临床观察研究

发布时间：2018-01-10 11:13

本文关键词：双酚A与女童单纯乳房早发育及中枢性性早熟关系的临床观察研究　出处：《苏州大学》2013年硕士论文　论文类型：学位论文

【摘要】：研究背景近些年来儿童青春发育呈现出提前发育的趋势，性早熟受到越来越多人的关注。性早熟的病因很多，目前认为环境内分泌干扰物（Environmentalendocrine-disrupting chemicals,EDCs）是引起性早熟的原因之一。文献报道双酚A（BisphenolA，BPA）作为环境内分泌干扰物的一种，能干扰正常的内分泌活动，动物实验中发现新生鼠长期低剂量BPA的暴露会引起性发育提前，雌性更加敏感。但迄今为止BPA对2岁以下女童单纯乳房发育（Permature Thelarche,PT）的影响及BPA在6-8岁女童单纯乳房发育及中枢性性早熟（Central precocious puberty,CPP）中的影响报道甚少，仍然不清楚其对2岁以下女童乳房发育及中枢性性早熟有无影响，而且BPA在下丘脑或其他组织中可能通过何种途径作用于靶细胞的机制并不明确。研究目的从临床角度观察研究BPA对2岁以下女童单纯乳房发育的影响及探讨BPA在6-8岁女童单纯乳房发育及中枢性性早熟中的关系，并探讨其可能的机制及原因。研究方法1.选择内分泌门诊就诊的6月---2岁PT40例，选择同期6月--2岁无乳房发育女童32例作为对照组，测量身高体重，询问喂养情况，利用高效液相色谱串联质谱法（HPLC-MS-MS）进行血清BPA浓度测定，利用化学发光法进行两组血清性激素浓度测定，比较两组差异及分析BPA与性激素之间相关性。 2.选择我院内分泌门诊就诊的6-8岁性早熟女童，平均根据性早熟的诊断标准及分类标准将性早熟女童分为CPP组47例及PT组56例，选择同期6-8岁无青春发育的女童53例作为对照组，测量身高体重，利用HPLC-MS-MS方法测定各组BPA浓度，用化学发光法进行PT组及CPP组性激素水平测定，用酶联免疫吸附法测定各组血清Kisspeptin浓度，比较三组差异、分析BPA与性激素、Kisspeptin之间相关性。研究结果1.6月---2岁女童PT组血清BPA检出率67.5%，浓度13.95±1.187ng/ml,高于正常对照组血清BPA检出率30.9%,浓度8.036±0.548ng/ml，，两组有统计学意义（P0.05）。两组血清卵泡刺激素（Follicle-stimulating hormone, FSH）,泌乳素（Prolactin,PRL）浓度无统计学差异(P0.05)，乳房发育组E2检出率（50%）高于正常对照组（18.75%）（P0.05），乳房发育组黄体生成素（Luteotrophic hormone,LH）检出率（47.5%）高于正常对照组（0.00）（P0.001）。两组BPA浓度与FSH浓度无相关性（r=0.179)、两组BPA浓度与PRL浓度也无相关性（r=0.279），BPA浓度与E2和LH有相关性（P0.05）。 2．6-8岁CPP组BPA的检出率95.83%，BPA浓度31.94±7.302ng/ml,PT组BPA检出率82.14%,浓度15.57±1.426ng/ml，正常对照组BPA检出率58.5%,浓度9.912±0.736ng/ml, CPP组BPA检出率及BPA浓度高于PT组（P 0.05）及正常对照组（P 0.01），PT组BPA检出率高于正常对照组，BPA浓度与正常对照组比较无统计学差异，（P0.05）。CPP组Kisspeptin浓度327.2±30.11pg/ml高于PT组224.2±19.81pg/m（lP 0.01）及正常对照组244.2±17.47pg/m（lP 0.05），PT组Kisspeptin浓度与正常对照组比较无统计学差异，（P0.05）。CPP组雌二醇（Estradiol,E2）浓度37.69±3.508pg/ml，高于PT组E2浓度27.44±2.002pg/ml,(P 0.01)。BPA浓度与Kisspeptin、LH、FSH浓度无相关性(P0.05)，BPA浓度与E2浓度有正相关性(P0.05)。研究结论.6月--2岁女童存在BPA的暴露。BPA暴露可能是6月--2岁女童出现乳房发育的原因之一。6月--2岁女童BPA的暴露可能影响LH及E2的分泌。6-8岁女童性早熟的发生与BPA的暴露有关，BPA的暴露可能是中枢性性早熟的原因之一。6-8岁性早熟女童BPA的暴露可能使E2的分泌增加，但与LH、FSH浓度无线性相关。BPA可能并非通过影响Kisspeptin蛋白表达来导致血清E2的升高从而对性早熟产生影响。
[Abstract]:Background in recent years shows early puberty development in children with precocious puberty development trend, attracted more and more attention. The cause of precocious puberty, the environmental endocrine disruptors (Environmentalendocrine-disrupting chemicals EDCs) is one of the reasons causing precocious puberty. Reports of bisphenol A (BisphenolA, BPA) as a kind of environmental endocrine disruptors that can interfere with normal endocrine activity, animal experiments found that exposure of neonatal rats with long-term low dose BPA can cause early puberty, female is more sensitive. But so far the BPA on the 2 girls under the age of pure breast development (Permature Thelarche, PT) and the effect of BPA in the 6-8 year old girl pure breast development and central precocious puberty (Central precocious puberty, CPP) the effect of report is very little, still not clear on the 2 girls under the age of breast development and there is no central precocious puberty The mechanism of BPA in the hypothalamus or other tissues that may act on the target cells is not clear.
The purpose of this study is to observe the effect of BPA on the development of breast in girls under 2 years old, and to explore the relationship between BPA and simple breast development and central precocious puberty in 6-8 year old girls.
Methods 1. selected endocrine clinic in June ---2 years PT40 cases, select the same period of June --2 years without breast development in girls in 32 cases as control group, measurement of height and weight, about feeding, using high performance liquid chromatography tandem mass spectrometry (HPLC-MS-MS) for determination of serum BPA concentration, luminescence serum sex hormone levels in two groups were measured the use of chemical analysis, the difference between the two groups and between BPA and sex hormone dependence.
2. select the endocrine clinic in our hospital 6-8 year old girls with precocious puberty, precocious girls average will be divided into 47 cases of group CPP and group PT 56 cases according to the diagnostic criteria of sexual precocity and classification standard, select the same period in 6-8 years without puberty girls in 53 cases as control group, height and weight were measured, using the HPLC-MS-MS method for the determination of the determination of BPA concentration, PT group and CPP group of sex hormone levels by chemiluminescence method, determination of serum Kisspeptin concentration by enzyme-linked immunosorbent assay, the difference between the three groups, analysis of BPA and Kisspeptin. The correlation between sex hormones.
Results 1.6 months ---2 year old girl group PT serum BPA positive rate was 67.5%, the concentration of 1.187ng/ml + 13.95, higher than the normal control group serum BPA positive rate was 30.9%, the concentration of 8.036 + 0.548ng/ml, two groups have statistical significance (P0.05). Serum follicle stimulating hormone (Follicle-stimulating group two hormone, FSH), prolactin (Prolactin, PRL) there was no significant difference in the concentration (P0.05), breast development group E2 positive rate (50%) higher than the normal control group (18.75%) (P0.05), breast development group of luteinizing hormone (Luteotrophic hormone, LH) detection rate (47.5%) and Gao Yuzheng (0) normal control group (P0.001). There was no correlation between BPA concentration and FSH concentration of two group (r=0.179), BPA concentration and PRL concentration of two groups have no correlation (r=0.279), the concentration of BPA is correlated with E2 and LH (P0.05).
2.6-8 CPP group BPA positive rate was 95.83%, the concentration of BPA 31.94 + 7.302ng/ml PT group, BPA positive rate was 82.14%, the concentration of 15.57 + 1.426ng/ml, the control group BPA positive rate was 58.5%, the concentration of 0.736ng/ml 9.912 + CPP group, the detection rate of BPA and BPA were higher in PT group (P 0.05) and normal control group (P 0.01) in group PT, the detection rate of BPA is higher than the normal control group, no significant differences between the BPA concentration and the normal control group, group.CPP (P0.05) concentration of Kisspeptin 327.2 + 30.11pg/ml 224.2 + 19.81pg/m higher than that of group PT (lP 0.01) and normal control group 244.2 + 17.47pg/m (lP 0.05), there was no statistical difference between PT group and normal Kisspeptin concentration the control group (P0.05),.CPP group (Estradiol, E2) estradiol concentration was 37.69 + 3.508pg/ml, E2 concentration higher than 27.44 in group PT + 2.002pg/ml (P, 0.01).BPA concentration and Kisspeptin, LH, there is no correlation between the concentration of FSH (P0.05), there was a positive correlation between BPA concentration and E2 concentration (P0.05).
Conclusions.6 month --2 year old girl BPA exposure to.BPA exposure may be June --2 year old girl appeared breast development one of the reasons for.6 months --2 years old girl BPA exposure may influence the secretion of E2 and LH.6-8 year old girls with precocious puberty associated with BPA exposure, BPA exposure may be exposed to central precocious puberty one of the reasons why.6-8 year old girls with precocious puberty BPA may make the secretion of E2 increased, but the concentration of FSH and LH, there was no correlation between the.BPA may not lead to the increase of serum E2 of precocious effect by influencing the expression of Kisspeptin protein.

【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R725.8

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