Abstract: The objective of this study is to explore the protective effect and mechanisms of grape seed proanthocyanidin extract (GSPE) against oxidative stress of HUVEC-12 cells induced by high glucose.HUVEC-12 cell model induced by high glucose was established.The proliferation of HUVEC-12 cells were evaluated.The levels of reactive oxygen species (ROS),lactate dehydrogenase (LDH) and superoxide superoxide dismutase (SOD) were assayed.Both mRNA expression levels and protein expression levels of Nrf2/ARE signaling pathway related genes were detected.The results showed that GSPE intervention can improve the antioxidant capacity of HUVEC-12 cells significantly,decrease the ROS levels in cells induced by high glucose,improve the SOD activity and the cell vitality in a dose-dependent effect (P<0.05).The analysis showed that GSPE can also increase the mRNA expression levels of Nrf2,GSH-Px, HO-1, -GCS, NQO1 and protein contents of HO-1,NQO1.The results indicated that GSPE may protect against the oxidative damage of HUVEC-12 cells induced by high glucose via the activation of Nrf2/ARE signal pathway.

Key words: grape seed proanthocyanidin extract, high glucose, Nrf2/ARE pathway, HUVEC-12 cell