重点实验室学术带头人免疫毒性研究文章

　　

生物通综合，中国科学院动物研究所动物生态与保护生物学重点实验室学术带头人戴家银带领的研究小组在免疫毒性方面的研究取得进展，相关成果文章Alterations of Cytokines and MAPK Signaling Pathways Are Related to the Immunotoxic Effect of Perfluorononanoic Acid发表在《Toxicological Sciences》（IF=3.814）上。

 

全氟有机物（Perfluorinated compounds, PFCs）属于一类新型持久性有机污染物，广泛应用于民用和工业产品。PFCs具有持久性、生物累积性、毒性以及能长距离迁移的特性。目前，在世界各地采集的环境样品、多种野生动物血清及组织样品（包括北极圈的生物）和人类体内都已检测到多种PFCs。PFCs在我国也已造成广泛污染，如我国部分省份人群血清全氟辛磺酸（PFOS）浓度明显高于发达国家；在我国圈养大熊猫等多种濒危动物血清中均检出全氟辛酸（PFOA）和PFOS；在污染区域的鱼类体内检出包括十碳全氟羧酸在内的7种PFCs。由于PFCs具有多种毒性，对生态环境和人体健康产生影响受到普遍关注，因此，对PFCs研究已成为环境科学和生态毒理学研究领域的热点课题之一。

 

动物研究所戴家银研究组发现全氟壬酸（PFNA，九碳链长的PFCs）的暴露可导致大鼠淋巴器官萎缩、影响淋巴细胞分泌细胞因子、刺激血清糖皮质激素（GC）水平增加，从而产生一定程度的免疫毒性。此外，胸腺细胞PPARα、PPARγ的表达上调，MAPK激酶（JNK及p38）在基因水平和蛋白水平均显著上调，抗凋亡基因Bcl2表达抑制，最终导致淋巴细胞大量产生凋亡。本研究初步揭示了PFCs类化合物的免疫毒性及其作用的分子机制。

 

生物通推荐原文检索：Alterations of Cytokines and MAPK Signaling Pathways Are Related to the Immunotoxic Effect of Perfluorononanoic Acid

【Abstract】

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.

 

戴家银，博士，中国科学院动物研究所研究员，2005年中科院动物所"****"入选者。1988年在安徽大学获理学学士学位；1996年在厦门大学获理学硕士学位；1999年在南京大学获博士学位。1988年7月－1993年7月在安徽科技学院生化教研室任教。1999-2000年在同济大学污染控制与资源化研究国家重点实验室从事博士后研究工作；2000-2001年在美国得克萨斯州立大学加尔维斯敦医学分校人类生物化学和遗传学系从事生物化学博士后研究；2001-2004年在美国康乃尔大学医学院生物化学系从事生物化学博士后研究。主要从事分子生态毒理学、生物化学以及环境化学研究。曾参与国家自然科学重点基金项目“部分有机物定量结构－活性相关研究”，及国际合作项目“中国东部发达地区饮用水源多氯有机物的调查及风险评价”，取得了很好的科研成果。目前，在研项目有中国科学院知识创新工程重要方向性项目“持久性有机污染物（POPs）的分子生态毒理效应及其生物可降解性研究”。 几年来，在国内外核心杂志上发表论文30篇，其中第一作者12篇论文被SCI收录，SCI论文被国际同行引用50多次。

 

所属研究组：生态毒理学研究组