砷致肝损伤已成为地方性砷中毒突出问题之一，但目前砷致肝损伤机制尚不明确并缺乏有效干预药物，至今尚未完全得到控制。肝细胞衰老可促进肝损伤等肝脏疾病发生发展，但砷是否可诱导肝细胞发生衰老及其机制尚未见相关报道，对该问题的探究可望成为砷中毒肝损伤防治的关键。研究显示，ETS-1与细胞衰老有关，但其调控机制尚不清楚。申请人及课题组研究表明砷可诱导人肝细胞衰老并上调ETS-1表达及抑制E2F1活性，推测ETS-1及其下游p16/Rb/E2F1通路可能介导了砷对肝细胞衰老的影响。另外，课题组前期研究结果表明银杏叶提取物（GBE）对砷致肝损伤有较好的干预作用，且GBE对砷诱导的L-02细胞衰老具有很好的抗衰老功效。因此，本项目拟采用银杏叶提取物进行干预研究，进一步探讨该通路在砷致肝细胞衰老中的作用；并采用GBE进行干预，探讨其在砷暴露下对肝细胞衰老的影响和机制，为地方性砷中毒肝损伤的防治提供新实验依据。

Arsenic-induced liver damage has become one of the most problems of endemic arsenism. However, the mechanism of arsenic-induced liver damage is still unclear and there is a lack of effective intervention drugs and it has not been completely controlled yet. Studies have shown that hepatocellular senescence can promote the occurrence and development of liver diseases such as liver injury, but whether arsenic can induce hepatocellular senescence and its mechanism have not been reported yet. The exploration of this problem is expected to be the key to the prevention and treatment of liver injury caused by arsenic exposure. Studies have shown that ETS-1 is associated with cellular senescence, but the mechanism by which it regulates cellular senescence remains unclear. Our previous studies have shown that arsenic can induce senescence , up-regulate the expression of ETS-1 and inhibit the activity of E2F1 in human liver cells, suggesting that ETS-1 and its downstream p16/Rb/E2F1 signaling pathway may mediate the effect of arsenic on hepatocellular senescence. Moreover, Our previous studies have showed that ginkgo biloba extract (GBE) has a better intervention effect on arsenic-induced live damage and has a good anti-senescence effect on arsenic-induced senescence in L-02 cells. Therefore, this project intends to use the extract of ginkgo biloba for intervention research, to further investigate the role of this pathway in arsenic-induced hepatocyte senescence. Then investigate the influence of GBE on hepatocyte senescence and mechanism under arsenic exposure to provide new experimental basis to prevent the liver damage of endemic arsenism.