Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.
Biol Trace Elem Res. 2013 Feb;151(2):269-76. doi: 10.1007/s12011-012-9558-7. Epub 2012 Dec 11.
Although studies have shown that arsenic exposure can induce apoptosis in a variety of cells, the exact molecular mechanism of chronic arsenicosis remains unclear. Based on our previous study on human serum, the present study was to determine whether pigment epithelium-derived factor (PEDF) plays a role in the damage induced by chronic arsenic exposure in a rat model and to explore the possible signaling pathway involved. Thirty male Wistar rats were randomly divided into three groups and the arsenite doses administered were 0, 10, and 50 mg/L, respectively. The experiment lasted for 6 months. Our results showed that level of arsenic increased significantly in serum, liver, brain, and kidney in arsenic-exposed groups. It was indicated that PEDF protein was widely distributed in the cytoplasm of various types of cells in liver, brain, and kidney. PEDF protein level was only changed when the arsenite dose reached 50 mg/L in liver and brain, whereas it was not changed in the kidney. In order to investigate the possible mechanism of PEDF-exerted damages upon arsenite exposure, apoptosis in liver and brain was assessed. The proportion of apoptotic cells gradually increased with increasing arsenic administration. The ratio of Bax/Bcl-2 in the high arsenic group (50 mg/L) was significantly higher than that in the control group. Therefore, we thought PEDF played a role in cell apoptosis of liver and brain which induced by sodium arsenite exposure, and the results also demonstrated that Bax and Bcl-2 might be two key targets in the action of PEDF.
尽管研究表明砷暴露可以诱导多种细胞凋亡，但慢性砷中毒的确切分子机制仍不清楚。基于我们之前对人血清的研究，本研究旨在确定色素上皮衍生因子（PEDF）是否在慢性砷暴露诱导的大鼠模型损伤中发挥作用，并探讨可能涉及的信号通路。
将 30 只雄性 Wistar 大鼠随机分为三组，分别给予亚砷酸钠剂量 0、10 和 50mg/L，实验持续 6 个月。结果表明，暴露组血清、肝、脑、肾中砷含量显著升高。结果表明，PEDF 蛋白广泛分布于肝、脑、肾中各种类型细胞的细胞质中。只有当肝和脑中的砷酸钠剂量达到 50mg/L 时，PEDF 蛋白水平才发生变化，而在肾脏中则没有变化。为了探讨 PEDF 在亚砷酸钠暴露下发挥作用的可能机制，评估了肝和脑中的细胞凋亡。随着砷处理的增加，凋亡细胞的比例逐渐增加。高砷组（50mg/L）的 Bax/Bcl-2 比值明显高于对照组。因此，我们认为 PEDF 在亚砷酸钠暴露诱导的肝和脑细胞凋亡中发挥作用，结果还表明 Bax 和 Bcl-2 可能是 PEDF 作用的两个关键靶点。
