色素上皮衍生因子（PEDF）在砷致血管内皮功能失调中的作用机制研究

Endemic arsenicosis is one of the key endemic diseases which threatens human health seriously. High arsenic exposure would damage to other organ before appearing typical “Trilogy of skin” that were occult at first and were not easy to be found. However, the damage would affect the quality of life seriously. In recent years, the hazards of arsenic on cardiovascular system were confirmed and were paid much attention by many researchers. Combined with the previous findings that the level of PEDF in serum was significantly elevated in high arsenic exposed human and rats, and it was found that the PEDF played a certain role in arsenic-induced cell apoptosis of liver and brain in a rat model. Based on the above, we proposed a scientific hypothesis as followings: PEDF could protect vascular endothelial function from arsenic from two aspects.(1)PEDF could inhibit the way of NADPH oxidase /ROS/eNOS/NO through role of antioxidation.(2) PEDF selectively induces endothelial cell apoptosis through pathways of Fas/FasL/p38MAPK/PPARγ/p53 and p53/Bax/Bcl-2. We plan to testify the aboving hypothesis through animal and cell experiment, it would have important significance on clarifying the mechanism of cardiovascular disease caused by arsenic, and would provide new scientific theory for the prevention and control arsenicosis.

地方性砷中毒严重威胁人类健康，是我国重点防治地方病之一。高砷暴露在引起典型的“皮肤三联症”之前，即可引起其他器官系统的损伤，这些病变起病隐匿，不易被发觉，但会严重影响生活质量。近年来，砷对心血管系统的危害逐渐引起广大科研工作者的认可和关注。结合本课题组前期研究，在慢性高砷暴露人群和实验动物均发现血清中PEDF的含量明显升高，并发现PEDF在砷诱导的大鼠肝脑细胞凋亡中发挥一定的作用，在此基础上提出科学假设：PEDF从两方面发挥对砷致血管内皮功能失调的保护作用。（1）PEDF通过抗氧化作用，抑制NADPH氧化酶/ROS/eNOS/NO途径；（2）PEDF选择性地诱导血管内皮细胞凋亡途径Fas/FasL/p38 MAPK/PPARγ/p53和p53/Bax/Bcl-2。本研究拟通过动物实验和细胞实验相结合，证明上述假设，对于阐明砷致心血管疾病发病机制具有重要意义，将为砷中毒防治提供新的科学依据。

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