持久性有機污染物全氟辛烷磺酸（PFOS）对糖尿病肾病的影响

项目名称： 持久性有機污染物全氟辛烷磺酸（PFOS）对糖尿病肾病的影响

项目编号： No.21477101

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 化学工业

项目作者： 钟志刚

作者单位： 香港浸会大学深圳研究院

项目金额： 90万元

中文摘要： 虽然TGF-β信号通路在糖尿病肾病发展过程中起到重要的作用，但持久性有机污染物会否影响TGF-β信号通路尚未阐明。全氟辛烷磺酸（PFOS）是中国一新兴持久性有机污染物。PFOS在接触后很容易积累在肾脏。本课题组通过对在高糖刺激下，首次发现PFOS加重肾小管上皮细胞纤维化、炎症、氧化应激及细胞肥大，并激活TGF-β信号通路。另外，PFOS促进了在阿霉素肾病小鼠模型肾脏损伤。基于前期研究，我们假设PFOS通过诱发炎症，纤维化、氧化应激和肾脏肥大增加肾脏在糖尿病肾病的损伤。因此，我们将首先确定在体外糖尿病条件下PFOS对肾纤维化，肥大，氧化应激和炎症的影响。并研究PFOS如何影响TGF-β信号机制及相关的代谢途径。更利用2型糖尿病小鼠模型去验证PFOS对肾损伤的影响。最后，将利用糖尿病肾病病人的血液及尿液样本来确定PFOS的水平与糖尿病肾病的相关性。本课题将阐明环境污染物怎样与糖尿病肾病有关。

中文关键词： 代谢调控；持久性有机污染物；糖尿病肾病；转化生长因子-β

英文摘要： Diabetic nephropathy (DN) is the leading cause of end stage renal disease. TGF-β signaling pathway plays an important role in the process of development of diabetic nephropathy but how persistent organic pollutants (POP) affects TGF-β signaling pathway during renal injury has not been elucidated. Perfluorooctane sulfonate (PFOS) is one emerging POP in China. PFOS is readily absorbed after oral exposure and accumulates primarily in the serum, kidney, and liver. Toxicological studies on animals indicate its potential developmental, reproductive and systematic effect. A novel and potentially important preliminary finding was that PFOS enhanced expression of markers for fibrosis, inflammation, hypertrophy and oxidative stress in renal tubular epithelial cells during diabetic condition. PFOS also promoted the activation of TGF-β signaling. Dietary intake of PFOS promoted the renal injury in the mouse model of Adriamycin nephropathy. Based on these findings, we hypothesize that PFOS may play an essential role in enhancing renal injury by increasing inflammation, fibrosis, hypertrophy, and oxidative stress during the progression of diabetic nephropathy. To test this hypothesis, we will firstly determine the effects of PFOS in renal fibrosis, hypertrophy, oxidative stress, and inflammation under diabetic condition in vitro. We will then examine how PFOS affects TGF-β signaling and related metabolic pathways under diabetic condition in vitro. Next, we will validate the effects of PFOS on renal injury during DN in type 2 diabetic mouse models. Finally, we will determine the correlation of PFOS levels in serum and urine with occurrence of DN in human patients. This novel study is significant because an identification of the effects of PFOS in DN will identify how an environmental pollutant is associated with renal injury in DN. These findings may suggest the potential health risk to be concerned due to the toxicological effects of PFOS as a ubiquitous compound in the environment.

英文关键词： metabolomics;Persistent Organic Polluants;Diabetic nephropathy;TGF-β