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围产期暴露于溴化阻燃剂六溴环十二烷(HBCD)对大鼠发育中免疫系统的影响

[Effects of perinatal exposure to the brominated flame-retardant hexabromocyclododecane (HBCD) on the developing immune system in rats].

作者信息

Hachisuka Akiko, Nakamura Ryosuke, Sato Yuji, Nakamura Rika, Shibutani Makoto, Teshima Reiko

出版信息

Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku. 2010(128):58-64.

PMID:21381397
Abstract

To evaluate the developmental immunotoxicity of brominated flame retardant, hexabromocyclododecane (HBCD) , maternal Sprague-Dawley rats were given HBCD at dietary concentrations of 0, 100, 1000, 10000 ppm from gestational day 10 to postnatal day 21 (postnatal week 3, PNW3). At PNW3 and PNW11, lymphocytes in the spleen, thymus, and peripheral blood of male pups were subjected to flow cytometric analyses for expression of surface markers (CD3, CD4, CD8a, CD25, CD45RA, CD71, and CD161 (NKRP1A)). The spleen and thymus weights, and number of white blood cells of two organs did not change between HBCD-exposed and control groups at PNW3 and PNW11. A significant decrease in thyroid hormone T3 and increase in serum albumin concentration were observed at PNW3 and lasted until PNW11. By flow cytometric analysis, the dramatic change was not observed in the population of the splenic and thymic T/B lymphocyte between the HBCD treated groups and control group. In the peripheral blood of BNW3 rats, the population of activated T cells was decreased and that of inactivated B cells was increased. And the population of NK cells in the spleen was decreased. All of these changes were mild in degree, and returned to the normal levels by PNW11. Production of anti-KLH IgG antibody after KLH immunization was reduced by the 10000 ppm HBCD treatment. These results suggest that developmental exposure to the highest dose of HBCD had a weak immunomodulatory effect at PNW3, and most of the immunomodulatory effect had recovered to normal levels by PNW11.

摘要

为评估溴化阻燃剂六溴环十二烷(HBCD)的发育免疫毒性,从妊娠第10天至出生后第21天(出生后第3周,PNW3),给孕斯普拉格-道利大鼠喂食浓度为0、100、1000、10000 ppm的HBCD。在PNW3和PNW11时,对雄性幼崽脾脏、胸腺和外周血中的淋巴细胞进行流式细胞术分析,检测表面标志物(CD3、CD4、CD8a、CD25、CD45RA、CD71和CD161(NKRP1A))的表达。在PNW3和PNW11时,HBCD暴露组和对照组之间的脾脏和胸腺重量以及两器官的白细胞数量没有变化。在PNW3时观察到甲状腺激素T3显著降低,血清白蛋白浓度升高,且持续至PNW11。通过流式细胞术分析,HBCD处理组和对照组之间脾脏和胸腺T/B淋巴细胞群体未观察到显著变化。在出生后第3周大鼠的外周血中,活化T细胞群体减少,失活B细胞群体增加。脾脏中NK细胞群体减少。所有这些变化程度较轻,并在PNW11时恢复到正常水平。经10000 ppm HBCD处理后,免疫接种钥孔血蓝蛋白(KLH)后抗KLH IgG抗体的产生减少。这些结果表明,在PNW3时,发育过程中暴露于最高剂量的HBCD具有较弱的免疫调节作用,且大部分免疫调节作用在PNW11时已恢复到正常水平。

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