线粒体氧化应激导致的功能障碍是引发高血压血管内皮损伤的主要病因。SIRT3 是线粒体内一种重要的去乙酰化酶。我们近期发现，在自发性和血管紧张素Ⅱ诱导的高血压动物模型中，主动脉内皮依赖性舒张功能减退，与线粒体去乙酰化酶SIRT3的表达下降及线粒体异常的融合和分裂相关联，推测去乙酰化酶SIRT3可能参与调控高血压血管内皮损伤。但对于SIRT3如何整合线粒体自由基代谢，调控内皮细胞的稳态机制尚不清楚。本项目以内皮细胞线粒体功能障碍为切入点，建立血管紧张素Ⅱ诱导高血压血管损伤模型，拟从细胞和整体水平上研究1）SIRT3在血管内皮损伤中的作用；2）SIRT3在修复线粒体抗氧化防御体系中的作用；3）SIRT3在逆转线粒体动力学异常变化中的作用。进一步阐明SIRT3-线粒体动力学-内皮细胞氧化损伤之间的关系，探寻高血压早期预防干预的新靶点，为防治高血压的发生发展开辟新的思路。

Mitochondrial dysfunction plays an important role in hypertensitive vascular injury.SIRT3 is an important deacetylase located in mitochondrion.We found that acetylcholine-induced vascular relaxation was impaired in accordance with decreased SIRT3 protein level and abnormal mitochondrial dynamics in spontaneously hypertensive rats and angiotension II infusion mice. We persume that SIRT3 may be involved in the protective effects on vascular injury. However, how SIRT3 integrate mitochondrial free radical generation and regulate endothelial cell homeostasis has not been clarified. The research aims to discover: 1)effects of SIRT3 on endothelial cell injury; 2)effects of SIRT3 on antioxidant capacity; 3)effects of SIRT3 on altertion of mitochondrial dynamic. This work would clarify the relationship among SIRT3, mitochondrial dynamic and vascular function. Activation of SIRT3 may be a promising target for the treatment of hypertension.