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壬基酚通过体内模拟雌激素作用诱导胸腺细胞凋亡通过 Fas/FasL 途径。

Nonylphenol induces thymocyte apoptosis through Fas/FasL pathway by mimicking estrogen in vivo.

机构信息

Immunology and Reproduction Biology Lab, Medical School & State Key Laboratory of Pharmaceutical Biotechology, Nanjing University, Nanjing 210093, PR China.

出版信息

Environ Toxicol Pharmacol. 2004 May;17(1):19-27. doi: 10.1016/j.etap.2004.01.006.

DOI:10.1016/j.etap.2004.01.006
PMID:21782709
Abstract

Nonylphenol (NP) is the final biodegradation product of nonylphenol polyethoxylates, which are widely used surfactants in domestic and industrial products. Nonylphenol has been reported to have estrogenic activity and shown to have potential reproductive toxicity. However, its influence on immune system function remains unclear. In this study, we investigated the effects of nonylphenol on apoptosis and Fas/FasL gene expression in rat thymus. Nonylphenol were given orally by gavages at 125, 250, and 375mg/kg per day. Negative and positive controls were treated with the vehicle and E(2) 10ng/kg per day, respectively. Atrophy of thymus was determined by in situ morphological examination using hematoxylin and eosin staining. Apoptotic cells were identified by terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labeling (TUNEL) assay. A semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method was used to analyze Fas and FasL mRNA levels. The results showed that both nonylphenol and E(2) increased the rates of apoptotic death; reduced the expression of Fas; enhanced the expression of FasL. These findings demonstrated that nonylphenol with estrogen-like activity might affect the regulation of the immune function through thymocyte apoptosis. This apoptosis was mediated by altering the expression of Fas and FasL mRNA.

摘要

壬基酚(NP)是壬基酚聚氧乙烯醚的最终生物降解产物,后者是广泛应用于家庭和工业产品中的表面活性剂。壬基酚具有雌激素活性,并有潜在的生殖毒性。然而,其对免疫系统功能的影响尚不清楚。本研究探讨了壬基酚对大鼠胸腺细胞凋亡和 Fas/FasL 基因表达的影响。壬基酚经灌胃给予大鼠 125、250 和 375mg/kg·d。阴性和阳性对照组分别用溶剂和 10ng/kg·d 的 E2 处理。采用苏木精-伊红染色的原位形态学检查确定胸腺萎缩。采用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记(TUNEL)检测鉴定凋亡细胞。采用半定量逆转录-聚合酶链反应(RT-PCR)方法分析 Fas 和 FasL mRNA 水平。结果表明,壬基酚和 E2 均增加了细胞凋亡率;降低 Fas 表达;增强 FasL 表达。这些发现表明,具有雌激素样活性的壬基酚可能通过胸腺细胞凋亡影响免疫功能的调节。这种凋亡是通过改变 Fas 和 FasL mRNA 的表达来介导的。

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引用本文的文献

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Para-nonylphenol impairs osteogenic differentiation of rat bone marrow mesenchymal stem cells by influencing the osteoblasts mineralization.对壬基酚通过影响成骨细胞矿化而损害大鼠骨髓间充质干细胞的成骨分化。
Iran J Basic Med Sci. 2012 Nov;15(6):1131-9.
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Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis.性腺激素在编程胸腺生成效率的发育变化和胸腺生成中的性二态性中的作用。
Immunol Res. 2012 Apr;52(1-2):7-19. doi: 10.1007/s12026-012-8278-6.
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Environmental toxin 4-nonylphenol and autoimmune diseases: using DNA microarray to examine genetic markers of cytokine expression.
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Arch Med Sci. 2010 Jun 30;6(3):321-7. doi: 10.5114/aoms.2010.14250.
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Elevation of inducible nitric oxide synthase and cyclooxygenase-2 expression in the mouse brain after chronic nonylphenol exposure.慢性壬基酚暴露后小鼠大脑中诱导型一氧化氮合酶和环氧化酶-2 表达的升高。
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