大剂量静脉应用Vitamin C（VitC）可有效减轻失血性休克等危重症的内皮功能损伤，但其机制仍不明确。我们前期研究证实大剂量VitC通过诱导血红素加氧酶-1（HO-1）减轻失血性休克大鼠的多器官损伤，预实验显示VitC对 HO-1上游调控蛋白去乙酰化酶SIRT1也有诱导作用，推测除了“消除活性氧化片段（ROS）及其病理损伤”这一传统机制外，大剂量VitC可能通过调控SIRT1及其下游靶点HO-1和NF-kB起保护作用，但具体机制仍需进一步探讨。在本项目中，我们建立失血性休克体内外模型，探索完全抑制ROS的VitC剂量VROS；观察不同剂量VitC（VROS为中间值）对SIRT1及HO-1和NF-kB的调控效应；用SiRNA等抑制技术，观察SIRT1是否介导VitC（剂量>VROS）的内皮保护功能。VitC是高效廉价的抗氧化剂，本项目的成功将为其在危重症临床应用提供新的基础理论依据。

Treatment with high dose Vitamin C was proved to relieve the endothelial injuries in critical care situations, such as hemorrhagic shock (HS), but the mechanism remains unclear. Our previous studies showed high dose Vitamin C relieved multiple organs injuries in hemorrhagic shock via heme oxygenase (HO)-1 induction, and our preliminary data indicated Vitamin C induced the expression of SIRT1 which is proved to be the upstream regulation protein of HO-1. We speculated beside the classic mechanism of “erasing the reactive oxidative species (ROS)”, the protecting mechanism of high dose Vitamin C may include the activation of SIRT1 as well as its downstream protein HO-1 and NF-kB. Anyway, more studies are in warrant. In this study, we establish the hemorrhagic shock model in vivo and in vitro and explore the dose of Vitamin C which significantly inhibit the ROS: VROS; we investigate the regulating effect of different dose of Vitamin C (the median value is VROS) on the expression of SIRT1, HO-1 and NF-kB; using SiRNA technique, we observed if SIRT1 play an mediation role on the relieving of HS related endothelial injuries by high dose Vitamin C. This study will provide new evidence for the applying in the critical care medicine of Vitamin C which is deemed as a cheap and high efficient antioxidant.