p53介导的细胞凋亡通路在燃煤砷污染致机体肝损伤中的作用及银杏叶片干预研究

Endemic arsenism caused by coal-burning is a special type of endemic arsenism only distributed in Guizhou and Shanxi province in China. In addition to the typical skin lesions, the patients also have serious liver damage and liver cirrhosis is one of the main reasons for this type of arsenic poisoning death. Due to the pathogenic mechanism of arsenic poisoning has not been fully elucidated, the mechanism of liver damage becomes the research focus. Early research found that the occurrence and development of liver injury caused by arsenic related to oxidative stress and apoptosis, and p53 which had functions of controlling cell cycle progression and apoptosis had complex cross-talk with the mechanism of arsenic poisoning. However, the effect of p53-mediated apoptosis on arsenic induced liver injury from coal-burning remains unclear. To further clarify the mechanism of arsenic induced liver injury from coal-burning, in our study, based on the population resource of arsenic poisoning caused by coal-burning in Guizhou province, combined with in vivo animal experiment and in vitro experiment, the regulation of p53 expression and the effects of p53-mediated apoptotic pathway on arsenic induced liver injury were investigated. In addition, the intervention effects and mechanism of Ginkgo biloba extract on arsenic induced liver injury were explored to provide new ideas and directions for the prevention and therapy strategies of arsenism.

燃煤型砷中毒是我国特有的一种地方性砷中毒病型，仅分布于贵州、陕西两省，患者除有典型皮肤病损外，尚具有严重的肝损伤，肝硬化是本型砷中毒死亡的主要原因之一。由于砷致病机制至今未明，燃煤型砷中毒肝损伤机制的研究成为该领域研究的热点。课题组前期研究发现，砷中毒肝损伤的发生、发展与氧化损伤和细胞凋亡有关，而具有调控细胞周期、细胞凋亡等功能的p53调控网络与砷毒作用机制有着密切联系。为了解砷致机体肝损伤与细胞凋亡和p53的关系，本研究充分利用贵州省特有的燃煤型砷中毒病型资源，从人群研究、动物实验和细胞实验三个体系，以肝脏为靶器官，探讨p53上游调控、p53表达及其介导的细胞凋亡通路在燃煤砷污染致肝损伤中的作用以及银杏叶片对其的干预作用，进而深入了解燃煤砷污染致机体肝损伤的机制，为地方性砷中毒的预防和治疗策略改进提供针对性依据。