目前人口老龄化是全球很多国家包括我国在内正在面临的棘手问题。与老龄化伴随而来的是大量心脑血管疾病、糖尿病、老年痴呆、癌症等疾病的发生。大量研究表明这些高发疾病都与活性氧密切相关。因此活性氧依赖性细胞死亡模式的分子调控机制及以其信号通路关键蛋白为靶点的新药研发日益受到关注。课题组以广泛存在于自然界的氢醌及常见环境污染物苯的主要代谢产物TGHQ作为环境相关性活性氧，选择与活性氧密切相关的 PARP-1 、Nrf2 等信号转导通路作为研究对象，深入阐明活性氧依赖性细胞死亡模式的调控机制，致力于研究活性氧涉及到的各种高发疾病机制、研究药物作用的细胞机制及环境毒物的毒性分子机制，不仅为苯及氢醌暴露引起的各类疾病的防治提供理论指导，而且为进一步理解活性氧信号在病理过程中的分子调控机制提供理论依据，为活性氧相关疾病（糖尿病、血栓、肿瘤等）的靶点研究与新药研发奠定良好的基础。而且，课题组还结合计算机辅助药物设计进行纳豆激酶的抗血栓作用机制研究及其修饰改造，以提高其体内生物稳定性及其临床应用的安全性。此外，鉴于目前药物性肝损伤已经成为新药研发的严重障碍和影响人民群众的健康水平和生活质量的重要原因之一，课题组还结合药物代谢进行系列中药成分诱导的肝脏毒性机制研究。

Aging of populations is the characteristic and trendof global population development, which has become a worldwide issue, especiallyChina. This will bring us increasing numbers of pathological problems. Since thegeneration of reactive oxygen species (ROS) has been implicated in thepathogenesis of tumor, cardiovascular diseases, diabetes, Alzheimer’s disease,and many other pathological conditions, increasing attention has been drawn to the molecular mechanismstudy of ROS-dependent cell death modes. Here we employ TGHQ, a metabolite of hydroquinoneas an environment-related ROS to elucidate the modulation mechanism of ROS-dependentcell death modes by investigating PARP-1 and Nrf2, two most ROS-involving pathways,with the emphasis on comparing their respective signaling pathways betweenTGHQ-induced apoptotic and non-apoptotic cell death modes through combiningdifferent methods, including pharmacology, toxicology, proteomics, and computermodeling....