在各种肝脏疾病的发病机制中，由氧化应激所致的肝细胞氧化-还原稳态失衡是关键环节，传统中医药对肝病的辅助治疗大多针对该环节。文献报道植物黄酮可通过激活MAPK或(和)PI3K/Akt等多条激酶途径，诱导Nrf2介导的HO-1等细胞保护基因表达上调，恢复肝细胞氧化-还原稳态。新近研究发现，GSK-3β可使Nrf2结构中的丝氨酸磷酸化，进而抑制Nrf2对细胞保护基因的转录激活作用。因此，GSK-3β磷酸化失活可能是植物黄酮激活激酶途径与诱导Nrf2的中间环节。我们前期对槲皮素半乳糖苷Hyp的研究观察到明显肝保护效应，且与激活ERK和p38途径，促进Nrf2核转位有关，但是否涉及PI3K/Akt和GSK-3β尚未明确。本项目拟以Hyp为工具药、HO-1为代表酶，基于GSK-3β磷酸化失活及其调控，探讨植物黄酮的肝保护效应与机制，可为充分利用传统中医药宝库对抗氧化性肝损伤开拓新策略。

xidative stress-induced liver damage plays a vital role in the pathogenesis of various liver diseases. The adjuvant treatment on liver diseases provided by traditional Chinese medicine mostly for this point. Flavonoids have been reported to elicit liver protective effect against oxidative stress through activation of Nrf2 signaling pathways and involving a number of ubiquitous intracellular kinases, including the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/Akt (PI3K/Akt). Such kinases may act in isolation or in concert to facilitate Nrf2 nuclear translocation. Recent research has shown that, GSK-3β can make the serine phosphorylation of Nrf2, and then inhibit the upregulation of cytoprotective gene. Therefore GSK-3β might integrate these kinases pathways at the level of Nrf2 in the protective effect of flavonoids. Our preliminary study on hyperoside(Hyp), a naturally occurring quercetin-3-galactoside have found that it attenuated hydrogen peroxide-induced L02 cell damage via p38 and ERK-dependent Nrf2 signaling pathway. However, the role of PI3K/Akt and GSK-3β in hyperoside-mediated upregalation of antioxidant enzymes remains to be elucidated. The present study was designed to investigate whether GSK-3β is a common target for above kinase in Hyp-induced Nrf2 signaling pathway. The results will be helpful for full understanding the pharmacological effects and mechanisms of flavonoids and can also make use of traditional Chinese medicine to develop new strategies on the treatment of oxidative stress-induced liver injury.