妊娠期双酚A暴露对子代行为和认知发育的影响

近年来,不少研究证实妊娠期双酚A(BPA)暴露对动物和人类子代情绪症状(焦虑、抑郁)、社会行为及非社会行为、记忆及脑执行功能等方面存在影响。鉴于BPA在日常消费品中广泛存在,其安全性问题日益受到关注,欧盟、加拿大及美国早已禁止婴儿奶瓶使用含BPA材料。我国对BPA的研究起步较晚,本文将从动物实验和人群研究两方面,对妊娠期BPA暴露与子代行为和认知发育之间的研究进展及主要存在问题做简要综述。     

孕期双酚A暴露致子代心理行为发育改变的相关机制研究进展

双酚A(bisphenol A)是一种常见的环境内分泌干扰物(EDCs),它常用作聚碳酸酯塑料、聚苯乙烯树脂和牙科密封剂的原料。BPA的环境污染很广泛,可通过水和食物进入人体,95%人群的尿样能够检测到BPA。流行病学资料和动物实验研究表明,BPA能够快速穿透胎盘屏障和血脑屏障,并且孕期BPA暴露能够致子代心理行为发育改变。本文将重点从表观遗传学、基因组与非基因组效应、氧化应激、多巴胺系统、突触数量和可塑性改变等方面阐述孕期BPA暴露对子代心理行为发育影响的机制。     

妊娠期双酚A暴露对子代行为和认知发育的影响北大核心CSCD

近年来,不少研究证实妊娠期双酚A(BPA)暴露对动物和人类子代情绪症状(焦虑、抑郁)、社会行为及非社会行为、记忆及脑执行功能等方面存在影响。鉴于BPA在日常消费品中广泛存在,其安全性问题日益受到关注,欧盟、加拿大及美国早已禁止婴儿奶瓶使用含BPA材料。我国对BPA的研究起步较晚,本文将从动物实验和人群研究两方面,对妊娠期BPA暴露与子代行为和认知发育之间的研究进展及主要存在问题做简要综述。     

孕期双酚A暴露致子代神经行为损伤机制

双酚A作为一种环境内分泌干扰物,用于生产聚碳酸酯塑料和环氧树脂,日常生活中含双酚A产品的使用使得暴露持续存在,显著增加了人类健康风险。发育关键期双酚A暴露可损害神经系统发育,尤其是对认知和行为的影响,但研究尚存在争议。本综述旨在对孕期双酚A暴露致子代认知损伤及行为问题相关机制的新进展进行简要概述。     

未成年大鼠双酚A暴露对卵巢发育影响

目的探讨双酚A暴露对未成年雌性大鼠的卵巢发育影响。方法48只雌性未成年Wistar大鼠按体重随机分为4组,溶剂对照组和双酚A低、中、高3个剂量组,腹腔注射染毒,染毒剂量分别为10、40、160 mg/kg,对照组注射橄榄油10 ml/kg,每天1次,连续8 d;称重后处死各组大鼠,取卵巢和子宫称重并计算脏器系数,测定血清雌二醇和孕酮水平,制作卵巢组织连续切片,计数各级卵泡数量。结果中、高剂量组卵巢脏器系数分别为(0.45±0.109)、(0.36±0.196)mg/g,均低于对照组的(0.71±0.126)mg/g,差异有统计学意义(P<0.01);血清雌二醇和孕酮水平随染毒剂量增高呈下降趋势,中、高剂量双酚A组孕酮水平(10.54、12.93 nmol/L)与对照组(43.65 nmol/L)比较,差异均有统计学意义(P<0.01);双酚A暴露可引起卵巢原始/初级卵泡比例减少,闭锁卵泡比例增加,中、高剂量组与对照组卵泡构成比差异均有统计学意义(P<0.01)。结论双酚A对未成年大鼠卵巢发育具有一定抑制作用,其机制可能与闭锁卵泡比例增加有关。     

围生期双酚A暴露对F1雄性子代大鼠脑发育的影响

目的研究围生期双酚A暴露对F1雄性子代大鼠出生后不同时期脑发育病理形态学的影响。方法对SD大鼠的母鼠从妊娠第11天直至产后断乳期染毒双酚A犤2,20,100mg/(kg·d)犦,同时设立对照组。每个剂量组分别在出生后第1、5、10、15、21、30、45天各时相点各取6只F1雄性子代大鼠,迅速断头处死大鼠后,取脑组织固定包埋,进行组织病理学检测。结果组织病理学(HE染色)结果显示,出生后1～10d,3个双酚A染毒剂量组的F1雄性子代大鼠在脑组织形态学上未见异常改变。出生后15～30d各剂量组脑组织均有不同程度的异常改变,主要表现为海马CA3区锥体细胞和大脑皮质神经元发生核固缩变性,其中20和100g/(kg·d)组较为严重。在出生后45d海马CA3区和大脑皮质异常细胞减少,组织形态基本正常,但神经细胞总数减少。结论围生期暴露于双酚A可以影响F1雄性子代大鼠的脑发育,可以引起F1雄性子代大鼠在出生后脑的组织病理形态学改变,从而可能最终引起功能和后期行为的改变。     

孕期染毒双酚A对雄性子代生殖发育影响

目的 探讨母鼠孕期接触双酚A对子代雄鼠生殖发育的影响及作用机制.方法 将受孕SD雌鼠40只,随机分为双酚A0、10、50、250 mg/kg染毒组,以2 mL/kg容积自受孕第5d灌胃染毒至第20d;孕第21 d每组处理5只孕鼠,检测母鼠血中性激素水平,胎鼠数、死胎数、胎鼠重和胎盘重,高效液相色谱法检测母鼠血及胎盘中双酚A含量,另5只孕鼠自然分娩,待雄性子鼠性成熟后检测血中性激素水平,生殖器官脏器系数、病理、精子质量.结果 10、50 mg/kg剂量组母鼠血清中雌二醇(E2)含量分别为1 780.78、1 680.10 pmol/L,明显高于对照组的1361.74pmol/L(P＜0.01),低、中、高3个染毒组睾酮(T)含量分别为5.55、4.76、6.79 nmol/L,明显高于对照组的3.20 nmol/L(P＜0.01);50、250mg/kg剂量组雄性子鼠附睾及前列腺脏器系数分别为0.297、0.325和0.153、0.173,均高于对照组(P＜0.01),镜下可见附睾间质及前列腺上皮有增生改变;250 mg/kg剂量组精子活动率为52.9%,明显低于对照组的67.4% (P ＜0.05).结论 孕期染毒双酚A对胎鼠发育无明显影响,但影响子鼠生殖器官发育和精子生成质量.     

甲醛染毒对大鼠子代神经行为发育的影响

[目的]探讨甲醛对大鼠子代早期神经行为发育的影响。[方法]进行两代一窝繁殖试验,选用体重110-130 g Wistar大鼠120只,随机分为4组,染毒浓度分别为,高浓度组:(119.6±15.4)mg/m3、中浓度组:(25.2±4.6)mg/m3、低浓度组:(4.8±1.3)mg/m3、对照组:室内空气。采用静式吸入法,每天染毒1 h,雄鼠连续染毒至交配后,雌鼠连续染毒至子代断乳,用一组行为毒理学方法检测雌、雄大鼠暴露于甲醛后子代生理及神经行为发育的情况。[结果]随着染毒浓度的增加,F1、F2代大鼠张耳、门齿萌出和开眼3项反映早期生理发育指标和平面翻正反射和悬崖回避试验阳性率呈逐渐降低趋势(P<0.05),学习、记忆达标训练次数和达标时间明显增多和延长(P<0.05),高浓度组学习达标时间、记忆达标时间分别高达(307.0±49.5)s、(279.7±42.35)s,持续游泳时间及耐缺氧时间均逐渐缩短,分别为(31.63±7.50)min、(43.40±4.94)min,P<0.05。[结论]甲醛对子代大鼠的神经系统有明显的损害作用。     

围生期暴露双酚A对母鼠及其成年期子代雌鼠血清氧化应激指标的影响

目的 探讨围生期暴露双酚A(bispheno1 A,BPA)对母鼠及其成年期雌性仔鼠氧化应激的影响.方法 将21只清洁级SD妊娠大鼠分为3组,分别为对照(含1％无水乙醇的水)组和低(1μg/ml)、高(10 μg/ml)浓度BPA组,每组7只.从妊娠第6天至哺乳期(出生后20d)结束,母鼠采用自由饮水方式进行染毒;断乳后,雌性仔鼠采用自由饮水方式继续喂养80 d.测定断乳后母鼠和100日龄雌性仔鼠血清丙二醛(MDA)含量和超氧化物歧化酶(SOD)活力及总抗氧化能力(T-AOC).结果 与对照组比较,断乳后各浓度BPA组母鼠血清MDA含量均增加,SOD活力和T-AOC水平均降低,差异有统计学意义(P＜0.05);高剂量BPA组母鼠血清MDA含量高于低剂量BPA组,差异有统计学意义(P＜0.05),且随着BPA暴露浓度的升高,断乳后母鼠血清MDA含量呈上升趋势,SOD活力和T-AOC水平均呈下降趋势.与对照组比较,出生后100d时各浓度BPA组雌性仔鼠血清MDA含量均增加,仅高浓度BPA组雌性仔鼠血清SOD活力和T-AOC水平均降低,差异有统计学意义(P＜0.01);且随着BPA暴露浓度的升高,出生后100d雌性仔鼠血清SOD活力和T-AOC水平均呈下降趋势.结论 围生期暴露BPA可引起母鼠和成年期雌性仔鼠氧化应激的发生.     

童年期双酚A暴露对女童青春期发育提前的影响

近年来,人群研究提示女童青春期发育有提前趋势,青春期提前已经成为不可忽视公共卫生问题和医学问题。导致青春期发育提前的因素除了社会经济改善、营养水平提升外,环境内分泌干扰物,尤其是双酚A(bisphenol A,BPA)的暴露对青春期发育提前的影响受到关注。本文将对双酚A暴露与女童青春期发育提前之间关系的研究进展进行综述,以期为进一步探讨女童青春期发育提前与环境内分泌机制提供理论依据。     

围生期暴露双酚A对青春期子代雌性大鼠糖代谢和血清炎症因子的影响

目的 探讨围生期暴露双酚A(bisphenol A,BPA)对青春期雌性子代大鼠体重、糖代谢及细胞炎症因子的影响.方法 将21只清洁级SD妊娠大鼠分为3组,分别为对照(含1％无水乙醇的水)组和低(1μg/ml)、高(10 μg/ml)浓度BPA暴露组,每组7只.从妊娠第6天至哺乳期(出生后20 d),母鼠采用自由饮水方式进行染毒;断乳后,雌性仔鼠采用自由饮水(不含BPA)方式继续喂养30 d.测定雌性仔鼠体重、空腹血糖、胰岛素水平及血清肿瘤坏死因子-α(tumornecrosis factor-α,TNF-α)和白介素6(interleukin-6,IL-6)水平,并计算胰岛素抵抗指数.结果 各浓度BPA暴露组雌性仔鼠体重、空腹血糖、血清胰岛素水平和胰岛素抵抗指数、TNF-α、IL-6水平均明显高于对照组,差异有统计学意义(P＜0,05,P＜0.01).结论 围生期暴露BPA可引起子代雌性大鼠体重增高和胰岛素抵抗,并可诱发机体炎症反应.     

农药敌匹硫磷和残杀威与内分泌干扰物双酚A联合暴露对细胞吞噬功能的影响

目的 探讨农药敌匹硫磷和残杀威与环境内分泌干扰物双酚A对细胞吞噬功能毒效应的联合作用方式.方法 采用荧光微球流式细胞仪检测技术,以吞噬百分率(PP)和吞噬指数(PI)为检测指标,观察无细胞毒性剂量的敌匹硫磷和双酚A、残杀威和双酚A联合暴露(受试物分别按等毒性比混合)对小鼠巨噬细胞RAW264.7吞噬功能的影响.敌匹硫磷与双酚A联合暴露终浓度分别为(0.4+0.1)、(3.6+0.7)、(36.2+7.2)、(43.4+8.7)、(52.1+10.4)、(62.5+12.5)、(75.0+15.0)μg/ml;残杀威与双酚A联合暴露终浓度分别为(0.2+2.0×10-2)、(2.4+0.2)、(23.7+2.0)、(35.6+3.0)、(53.3+4.4)、(80.0+6.7)、(120.0+10.0)μg/ml.以剂量-效应关系为基础,选择效应差异具有统计学意义的敌匹硫磷与双酚A、残杀威与双酚A剂量分别进行2×2完全析因实验,分析敌匹硫磷与双酚A、残杀威与双酚A的联合作用方式.结果 在联合暴露条件下,与对照组[PP为(23.6±2.2)%;PI为0.36±0.03]相比,敌匹硫磷+双酚A各剂量组[(52.1+10.4)、(62.5+12.5)、(75.0+15.0)μg/ml]均能提高细胞的PP[(29.0±1.4)%,t=3.89,P<0.05;(30.2±2.3)%,t=4.74,P<0.05;(35.0±3.4)%,t=8.21,P<0.05]和PI(0.43±0.03,t=3.86,P<0.05;0.41±0.02,t=2.95,P<0.05;0.46±0.03,t=5.34,P<0.05)水平;而残杀威+双酚A各剂量组[(35.6+3.0)、(53.3+4.4)、(80.0+6.7)、(120.0+10.0)μg/ml]则降低细胞的PP[(20.6±1.1)%,t=-3.00,P<0.05;(20.2±1.0)%,t=-3.42,P<0.05;(19.4±1.3)%,t=-4.23,P<0.05;(18.8±2.1)%,t=-4.81,P<0.05]和PI(0.31±0.01,t=-4.75,P<0.05;0.31±0.01,t=-4.58,P<0.05;0.30±0.01,t=-4.92,P<0.05;0.27±0.02,t=-7.80,P<0.05)水平.选择敌匹硫磷[60.0μg/ml,PP为(28.5±3.4)%,PI为0.49±0.07]与双酚A[12.0μg/ml,PP为(35.7±2.7)%,PI为0.67±0.07]、残杀威[48.0 μg/ml,PP为(28.1±2.2)%,PI为0.48±0.04]与双酚A[4.0μg/m1,PP为(34.4±2.7)%,PI为0.59±0.07],分别进行2×2析因设计实验.分析结果显.示,敌匹硫磷和双酚A对RAW264.7细胞的PP[(30.4±1.4)%]和PI(0.53±0.03)的影响存在交互作用(PP,F交互作用=6.22,P<0.05;PI,F交互作用=7.35,P<0.05),残杀威和双酚A之间亦存在交互作用[PP为(27.5±4.1)%,F交互作用=4.56,P<0.05;PI为0.46±0.08,F交互作用=11.13,P<0.05],均表现为拮抗作用.结论 敌匹硫磷与双酚A、残杀威与双酚A对RAW264.7细胞吞噬功能毒效应的联合作用方式均为拮抗作用.

Abstract：

Objective To explore the toxicity of joint exposure to diazinon,propoxur and bisphenol A on phagocytosis. Methods Flow cytometer was employed to detect the influence of diazinon and bisphenol A, propoxur and bisphenol A in mixture (mixed according to ratio of IC50) on mouse macrophage RAW264. 7 cells' function to phagocyte fluorescent microspheres, adopting the percentage of phagocytic cells (PP) and the phagocytic index (PI) as measurement indicators. The final concentrations of mixture of diazinou and bisphenol A were (0. 4 + 0. 1), (3.6 + 0. 7), (36. 2 + 7. 2), (43.4 + 8.7), (52.1 + 10.4),(62.5 + 12.5), (75.0 + 15.0) μg/ml; while those of mixture of propoxur and bisphenol A were (0.2+2.0×10-2),(2.4 +0.2), (23.7 +2.0),(35.6 +3.0),(53.3 +4.4),(80.0 +6.7),(120. 0 + 10.0) μg/ml. Then based on the dose-response relationship, a 2 × 2 factorial design was then carried out among different doses of mixture with statistical significance to statistically evaluate the interaction between diazinon and bisphenol A, propoxur and bisphenol A. Results After the joint exposure, compared to the control group (PP = (23.6 ± 2. 2) %; PI = 0. 36 ± 0. 03), any dose of the mixture of diazinon and bisphenol A ((52. 1 + 10. 4), (62. 5 + 12. 5), (75.0 + 15.0) μg/ml) could significantly increase the levels of PP ((29.0±1.4)%,t=3.89,P<0. 05; (30.2 ±2.3)%,t =4.74,P<0.05; (35.0±3.4)%,t=8.21,P <0. 05) and PI (0.43 ±0. 03,t=3.86,P <0. 05; 0.41 ±0. 02,t=2.95,P <0. 05; 0.46 ±0. 03, t = 5. 34, P < 0. 05); while that of propoxur and bisphenol A ((35.6 + 3.0), (53.3 + 4. 4), (80. 0 +6.7) ,(120.0 + 10.0) μg/ml) reduced the levels of PP ((20.6±1.1)% ,t=-3.00,P<0.05; (20.2±1.0)%,t=-3.42,P<0.05; (19.4±1.3)%,t=-4.23,P<0.05; (18.8±2.1)%,t=-4.81,P<0.05) and PI (0.31 ±0.01,t =-4.75,P<0.05; 0.31 ±0.01,t =-4.58,P<0.05; 0.30 ±0.01,t=-4. 92, P < 0. 05; 0. 27 ± 0. 02, t =-7. 80, P < 0. 05) on the contrary. The 2 × 2 factorial design was carried out between the mixture of diazinon (60. 0 μg/ml; PP = (28. 5 ± 3.4) %; PI = 0. 49 ± 0. 07) and bisphenol A (12.0 μg/ml; PP= (35.7 ± 2.7)%; PI= 0.67 ± 0.07), and the mixture of propoxur (48.0 μg/ml; PP= (28. 1 ±2.2)%; PI=0.48 ±0.04) and bisphenol A (4.0 μg/ml; PP= (34.4 ±2. 7) %; PI = 0. 59 ± 0. 07). The mixture of diazinon and bisphenol A (PP = (30. 4 ± 1.4) %, Finteraction=6. 22, P < 0.05; PI = 0. 53 ± 0. 03, Finteraction = 7. 35, P < 0. 05) and the mixture of propoxur and bisphenol A (PP= (27.5 ±4.1)%,Finteraction=4.56,P<0.05; PI = 0. 46 ± 0. 08, Finteraction=11.13,P<0.05) both showed a significant antagonistic interaction on phagocytosis of RAW264. 7 cell. Conclusion It is suggested that the interactions between diazinon & bisphenol A and propoxur & bisphenol A both played the antagonistic role on phagocytic function of macrophages in vitro.     

Effects of perinatal exposure to bisphenol A on brain neurotransmitters in female rat offspring

Pregnant Sprague-Dawley (CD IGS) rats were orally administered doses of bisphenol A (BPA) at 4, 40, and 400 mg/kg, from gestation days 6 to postnatal day 20. Neurotransmitters such as dopamine (DA) and serotonin (5HT) were extracted from the brains of dams and female offspring, and measured using liquid chromatography. BPA at 400 mg/kg was toxic and dosed rats died. At 3 wk after birth, brain levels of 3,4-dihydroxyphenylacetic acid (DOPAC, a DA metabolite), homovanillic acid (HVA, a DA metabolite), 5HT, 5-hydroxyindoleacetic acid (5HIAA, a 5HT metabolite) in female offspring were increased and the HVA/DA ratio was high in some brain areas of BPA-treated groups as compared with controls. At the age of 6 wk, levels of choline (Ch) in BPA-treated groups at 4 and 40 mg/kg were higher than control in all of eight brain areas. No changes were observed in acetylcholine (ACh) contents. In 9-wk-old offspring, changes in monoamines and metabolites were scattered and not great. At 3 wk after delivery, levels of 5HIAA in some brain areas of dams treated with BPA were higher than in control dams. Dose dependent increases in HVA and the HVA/DA ratio of the occipital cortex, and in the HVA/DA ratio of the frontal cortex were observed. The turnover of DA and 5HT was accelerated in 3-wk-old offspring and dams. BPA possesses very weak estrogenic activity. Changes in cerebral neurotransmitters observed in offspring and dams in this study may have been related to the estrogenic activity of BPA. However, further investigation is needed to examine the contribution of hormonal activity to such neurotransmitter changes.     

Intrauterine bisphenol A exposure leads to stimulatory effects on Sertoli cell number in rats

Using the optical disector for quantifying cell numbers, we investigated whether oral treatment of rats on days 6-21 of gestation with the weakly estrogenic bisphenol A (BPA, 0.1 or 50 mg/kg) or the highly estrogenic ethinyl estradiol (EE, 0.02 mg/kg) alters testicular histology, in those offspring 9-12 month of age. Since production of male germ cells depends on Sertoli cell number, possible changes in that parameter were investigated using unbiased stereology. Spermatogenesis was qualitatively normal in all groups. BPA increases Sertoli cell number per organ but not when expressed as per gram testis. EE did not affect cell number per organ but did affect numbers on a per gram testis basis due to a lowered testis weight. In contrast to the lowering of Sertoli cell numbers that might have been expected according to the estrogen hypothesis, intrauterine administration of these xenoestrogens in fact resulted in minor increases in Sertoli cell numbers and had no qualitative effect on spermatogenesis.     

Urinary bisphenol A concentrations in pregnant women

Bisphenol A is a chemical that is present in a number of products and types of food packaging. Prenatal exposure to bisphenol A may cause behavioural changes in young children. The aim of this study was to investigate exposure to bisphenol A in pregnant Australian women as a surrogate of neonatal exposure. First morning void urine samples were collected from 26 pregnant women at around week 38 of gestation. Bisphenol A was detectable in 85% of the samples analysed. The median concentration in this group of women was 2.41 μg/L with a range of <LOD – 5.66 μg/L. Women experiencing their first pregnancy had slightly higher urinary bisphenol A concentrations, as did women with a pre-pregnancy BMI of <25, however these relationships did not reach significance. This study provides the first information on bisphenol A exposure in Australia and reveals that pregnant women have measured biological concentrations of urinary bisphenol A similar to those reported for pregnant women in other developed countries. Given the potential impacts of prenatal bisphenol A exposure, further research in this area is warranted.     

基于生物监测的孕期双酚A暴露对雌激素稳态的影响

目的  探究孕妇双酚A (bisphenol A, BPA)暴露对孕期雌激素稳态的影响。方法  选择上海市嘉定区151名孕妇作为研究对象, 进行问卷调查和随机尿液收集。采用超高效液相色谱串联四级杆飞行时间质谱仪测定尿液中BPA和雌酮、17β-雌二醇、雌三醇浓度。在经尿肌酐校正、自然对数转换, 并且去除离群值后, 采用多元线性回归分析尿液中BPA暴露水平与雌激素关系。结果  孕妇尿样中BPA检出率为99.34%, 尿肌酐校正后浓度中位数为0.65 μg/g。年龄、孕周、家庭年总收入、二手烟接触情况和文化程度与尿液中BPA水平无关联。尿液中雌激素水平随孕期发展呈上升趋势。多元线性回归发现在全部孕妇中, 尿液中BPA水平与雌酮水平(β=0.171, 95%CI: 0.006~0.336)和17β-雌二醇水平(β=0.137, 95%CI: 0.000~0.274)呈正相关。在按孕期分层后, 发现孕晚期尿液中BPA水平与雌酮水平呈正相关(β=0.449, 95%CI: 0.014~0.884)。结论  上海市孕妇普遍暴露于BPA, 并且孕期BPA暴露水平可能影响雌激素稳态。     

孕期双酚A暴露对学龄前儿童情绪和行为问题的影响

目的 探讨孕期双酚A（BPA）暴露对学龄前儿童情绪和行为问题的远期影响效应。方法 研究样本源于中国安徽出生队列研究（China-Anhui Birth Cohort Study）的前瞻性随访人群。采用课题组编制的调查表收集孕妇和儿童的基本信息,运用固相萃取-同位素内标-高效液相色谱串联质谱法检测母亲孕期血清中游离的BPA含量。应用长处和困难问卷评估学龄前儿童的情绪和行为问题,最终纳入1 713对母子。运用多分类logistic回归模型分析孕期BPA暴露与学龄前儿童情绪和行为问题的病因关联。结果 1 713名学龄前儿童中,情绪症状异常检出率为6.48%,品行问题异常检出率为8.11%,多动/注意缺陷异常检出率为8.35%,同伴交往异常检出率为2.86%,亲社会行为问题异常检出率为11.38%,困难总分异常检出率为7.94%。按血清游离BPA浓度（ng/ml）三分位数法将研究对象分为低暴露组（≤ 0.120）、中暴露组（0.120OR=1.876,95% CI：1.161~3.029）,且在男童中表现更明显（OR=2.291,95% CI：1.126~4.661）。结论 母亲孕期高水平BPA暴露可能增加学龄前儿童品行问题异常的发生风险,且在男童中表现得更为明显。     

邻苯二甲酸酯宫内暴露对子代小鼠致肥作用的研究

目的:研究围产期宫内暴露邻苯二甲酸酯(MEHP)对子代小鼠肥胖的程序化作用。方法:不同剂量MEHP(0.05、0.25、0.5mg/kg体重)灌胃处理孕鼠做为低中高剂量组,等体积橄榄油灌胃处理的孕鼠做为对照组。处理周期为孕鼠妊娠第12天直至新生鼠出生后第7天。每周监测仔鼠体重直至第8周,并检测8周龄仔鼠的肝重、脂肪垫质量、血脂和血糖水平。结果:3组剂量MEHP宫内暴露均引起新生仔鼠体重增加(P<0.001);成年后(8周龄)雌性仔鼠体重接近对照组,而低剂量组成年雄性仔鼠体重明显高于对照组(P<0.01),附睾和肾周脂肪垫质量明显增加(P<0.001和P<0.01),血清总胆固醇、甘油三酯和血糖水平明显上升(P<0.01、P<0.05、P<0.001)。中高剂量对成年雄性仔鼠的体重、体脂组成、血脂和血糖水平无明显影响。结论:MEHP可以增加子代雄鼠肥胖发生风险,它可能作为一种潜在的化学诱导因子诱发肥胖及相关疾病发生。     

围产期铅暴露对新生大鼠血铅含量的影响

目的　了解铅通过母体对生长发育期仔代血铅的影响。方法　对不同浓度低水平铅暴露后的大鼠仔代的血铅进行测定。结果　铅可由母体经胎盘和乳汁传递给仔代。结论　胚胎期和哺乳期经胎盘和乳汁“染铅” ,是导致子代铅蓄积的重要原因。