全氟有機物（Perfluorinated compounds, PFCs）屬于一類新型持久性有機污染物,，廣泛應(yīng)用于民用和工業(yè)產(chǎn)品,。PFCs具有持久性、生物累積性,、毒性以及能長距離遷移的特性,。目前,，在世界各地采集的環(huán)境樣品、多種野生動物血清及組織樣品（包括北極圈的生物）和人類體內(nèi)都已檢測到多種PFCs,。PFCs在我國也已造成廣泛污染，如我國部分省份人群血清全氟辛磺酸（PFOS）濃度明顯高于發(fā)達國家,；在我國圈養(yǎng)大熊貓等多種瀕危動物血清中均檢出全氟辛酸（PFOA）和PFOS；在污染區(qū)域的魚類體內(nèi)檢出包括十碳全氟羧酸在內(nèi)的7種PFCs。由于PFCs具有多種毒性,，對生態(tài)環(huán)境和人體健康產(chǎn)生影響受到普遍關(guān)注,，因此,，對PFCs研究已成為環(huán)境科學(xué)和生態(tài)毒理學(xué)研究領(lǐng)域的熱點課題之一。
中國科學(xué)院動物研究所戴家銀研究組發(fā)現(xiàn)全氟壬酸（PFNA,，九碳鏈長的PFCs）的暴露可導(dǎo)致大鼠淋巴器官萎縮、影響淋巴細胞分泌細胞因子,、刺激血清糖皮質(zhì)激素（GC）水平增加,，從而產(chǎn)生一定程度的免疫毒性。此外,，胸腺細胞PPARα、PPARγ的表達上調(diào),，MAPK激酶（JNK及p38）在基因水平和蛋白水平均顯著上調(diào),，抗凋亡基因Bcl2表達抑制，最終導(dǎo)致淋巴細胞大量產(chǎn)生凋亡,。本研究初步揭示了PFCs類化合物的免疫毒性及其作用的分子機制。（生物谷Bioon.com）
生物谷推薦原始出處：
Toxicological Sciences 2009 108(2):367-376; doi:10.1093/toxsci/kfp019
Alterations of Cytokines and MAPK Signaling Pathways are Related to the Immunotoxic Effect of Perfluorononanoic Acid
Xuemei Fang*, Yixing Feng*, Zhimin Shi and Jiayin Dai*,1
* Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100190, China Graduate School of the Chinese Academy of Sciences, Beijing 100080, China
Perfluorononanoate (PFNA), a perfluorinated alkyl acid containing nine carbon chains, has been detected in abiotic and biotic matrices worldwide. Although a few studies have reported toxic effects of PFNA, little information of the mechanism has been offered. In this study, the effects of PFNA exposure on thymus and the related mechanisms were investigated. Male rats were orally dosed with 0, 1, 3, or 5 mg PFNA/kg/day for 14 days. A significant decrease of body weight and thymus weight were observed in the rats receiving 3 or 5 mg PFNA/kg/day. Histopathological examination revealed dose-dependent increases in thymocyte apoptosis. Rats receiving 3 or 5 mg PFNA/kg/day exhibited increased interleukin (IL)-1 and decreased IL-2 concentrations in sera, whereas elevated IL-4 and cortisol levels only occurred in the highest dose group. Quantitative real-time PCR indicated that expression of peroxisome proliferator–activated receptor alpha (PPAR-) was increased in the thymi of all dosed rats, and a similar trend occurred for PPAR- in the two highest dose groups. The mRNA levels of c-Jun NH2-terminal kinase (JNK), nuclear factor-kappa B, p65 subunit, and inhibitory protein IB were unchanged; however, increased and decreased mRNA levels of p38 kinase were found in rats exposed to 3 or 5 mg PFNA/kg/day, respectively. Decreased Bcl-2 mRNA levels were observed in rats receiving 5 mg PFNA/kg/day. A significant increase in protein levels of phospho-JNK was found in all PFNA-treated rats. Phospho-p38 was significantly enhanced in 1 and 3 mg PFNA/kg/day groups, whereas phospho-IB remained consistent in all rats studied. Together, these data suggested that apart from the activation of PPARs, PFNA exposure in rats lead to the alteration of serum cytokines, which subsequently activated mitogen-activated protein kinase signaling pathways and potentially modulated the immune system. Additionally, increased serum cortisol and decreased expression of Bcl-2 in thymus likely contributed to the PFNA-induced thymocyte apoptosis.
