心肌缺血再灌注损伤（MIRI）是临床面临的难题之一，寻找有效的干预手段治疗MIRI迫在眉睫。研究表明白藜芦醇（RSV）可有效减轻MIRI，但其分子机制尚未完全阐明。我们前期实验表明：RSV在MIRI过程中可上调其经典信号通路SITR1及其下游分子FOXO1的表达；RSV还可通过上调新信号通路VEGF-B/AKT/GSK3β及其下游抗氧化酶的表达拮抗MIRI。同时，文献表明GSK3β与FOXO1之间还存在着一定的联系。因此我们推测，RSV拮抗MIRI的作用是通过经典途径SIRT1及新途径VEGF-B的协同作用来完成的。我们拟在细胞，离体及整体水平，借助多种分子和细胞生物学技术手段，综合运用siRNA，基因敲除鼠等技术，探讨RSV的新作用通路VEGF-B与经典作用通路SIRT1之间的对话机制。本课题的立项将进一步完善RSV减轻MIRI的分子机制，为临床MIRI的防治提供新的思路和证据。

Myocardial ischemia-reperfusion injury (MIRI) is one of the difficulties in clinical work. Seeking effective interventions to treat MIRI is an urgent clinical requirement. Studies have shown that resveratrol (RSV) can effectively attenuate MIRI; however the molecular mechanism has not been fully elucidated. Our preliminary results showed that RSV could increase the expression of its classic signaling pathway (SIRT1) and its downstream molecule FOXO1 in the process of MIRI; RSV could also increase the expressions of its new signaling pathway (VEGF-B/AKT/GSK3β) and their downstream antioxidant enzymes to inhibit MIRI. Importantly, the literature indicated that there were certain relationships between GSK3β and FOXO1. Therefore, we speculate that RSV attenuates MIRI through the synergistic effect of VEGF-B and SIRT1 signaling pathway. We intend to make in vitro, ex vivo and in vivo MIRI models, using molecular and cellular biology techniques, and using siRNA and knockout mice to explore the crosstalk between VEGF-B and SIRT1 in RSV induced cardio-protection during MIRI. This project will further improve the understanding of molecular mechanism of RSV in MIRI, and provide new ideas and evidences of clinical prevention for MIRI.