Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), 157 Baojian Road, Harbin, 150081, China.
Biol Trace Elem Res. 2019 Aug;190(2):405-413. doi: 10.1007/s12011-018-1559-8. Epub 2018 Nov 3.
Water-borne arsenicosis is caused by the consumption of excess levels of inorganic arsenic from drinking water and is a worldwide public health issue. Arsenic exposure has recently attracted extensive attention due to its damage to the cardiovascular system. Vascular endothelial dysfunction (VED) is recognized as an important cause of cardiovascular diseases. Pigment epithelium-derived factor (PEDF) plays an important role in maintaining endothelial function, and our previous studies suggested that PEDF may have role in arsenic-induced damage. In the present study, we established subchronic arsenic exposure (3 months) rat model from drinking water at doses of 0, 2 mg/L, 10 mg/L, and 50 mg/L, respectively. The results showed that the endothelial cells of the aortic arch were obviously damaged, the apoptosis rate increased, the vWF and iNOS levels increased, and the NO and TNOS levels significantly decreased in the arsenic exposure groups. Regardless of serum or aortic arch endothelium, PEDF levels in the arsenic exposure groups decreased compared to the control group. The oxidative stress level and key proteins associated with apoptosis such as Fas, FasL, P53, and p-p38 were then detected to explore the detailed mechanisms. The results showed that the P53 and p-p38 levels significantly increased in the 10 mg/L and 50 mg/L groups compared to the control group. The MDA content in the arsenic exposure groups increased markedly, whereas the SOD activity decreased significantly with the increased arsenic dose. Taken together, our study is the first to find that PEDF plays a protective role in arsenic-induced endothelial dysfunction through anti-oxidation and anti-apoptosis, and p38 and P53 may be promising target proteins.
饮水型砷中毒是由于饮用水中摄入过量无机砷引起的，是一个全球性的公共卫生问题。砷暴露最近受到广泛关注，因为它会损害心血管系统。血管内皮功能障碍（VED）被认为是心血管疾病的重要原因。色素上皮衍生因子（PEDF）在维持内皮功能方面起着重要作用，我们之前的研究表明 PEDF 可能在砷诱导的损伤中发挥作用。在本研究中，我们通过饮用分别为 0、2mg/L、10mg/L 和 50mg/L 的水，建立了亚慢性砷暴露（3 个月）大鼠模型。结果表明，砷暴露组的主动脉弓内皮细胞明显受损，细胞凋亡率增加，vWF 和 iNOS 水平升高，NO 和 TNOS 水平显著降低。无论在血清还是主动脉弓内皮中，砷暴露组的 PEDF 水平均低于对照组。然后检测氧化应激水平和与凋亡相关的关键蛋白，如 Fas、FasL、P53 和 p-p38，以探讨其详细机制。结果表明，与对照组相比，10mg/L 和 50mg/L 组的 P53 和 p-p38 水平显著升高。砷暴露组的 MDA 含量明显增加，而 SOD 活性随砷剂量的增加而显著降低。综上所述，本研究首次发现 PEDF 通过抗氧化和抗凋亡在砷诱导的内皮功能障碍中发挥保护作用，p38 和 P53 可能是有前途的靶蛋白。
