Sirtuin 3 (Sirt3) is a member of the Sirtuin family proteins and known to regulate multiple physiological processes such as metabolism and aging. As stroke is an aging-related disease, in this work, we attempt to examine the role and potential mechanism of Sirt3 in regulating ischemic stroke by using a permanent middle cerebral artery occlusion (pMCAO) model in wild type (WT) and Sirt3 knockout (KO) mice, coupled with oxygen glucose deprivation (OGD) experiments in cultured primary astrocytes. Sirt3 deficiency aggravated neuronal cell apoptosis and neurological deficits after brain ischemia. In addition, Sirt3 KO mice showed more severe blood–brain barrier (BBB) disruption and inflammatory responses compared with WT group in the acute phase. Furthermore, specific overexpression of Sirt3 in astrocytes by injecting glial fibrillary acidic protein (GFAP)::Sirt3 virus in ischemic region showed protective effect against stroke-induced damage. Mechanistically, Sirt3 could regulate vascular endothelial growth factor (VEGF) expression by inhibiting hypoxia inducible factor-1α (HIF-1α) signaling after ischemia (OGD). Our results have shown that Sirt3 plays a protective role in ischemic stroke via regulating HIF-1α/VEGF signaling in astrocytes, and reversal of the Sirt3 expression at the acute phase could be a worthy direction for stroke therapy.

Sirtuin 3 (Sirt3) 是 Sirtuin 家族蛋白的成员，已知可调节多种生理过程，如新陈代谢和衰老。由于中风是一种与衰老相关的疾病，在这项工作中，我们试图通过使用野生型 (WT) 和 Sirt3 敲除的永久性大脑中动脉闭塞 (pMCAO) 模型来研究 Sirt3 在调节缺血性中风中的作用和潜在机制。 KO) 小鼠，再加上培养的原代星形胶质细胞中的氧糖剥夺 (OGD) 实验。Sirt3缺乏加重脑缺血后神经元细胞凋亡和神经功能缺损。此外，与 WT 组相比，Sirt3 KO 小鼠在急性期表现出更严重的血脑屏障（BBB）破坏和炎症反应。此外，通过在缺血区域注射胶质纤维酸性蛋白 (GFAP)::Sirt3 病毒，在星形胶质细胞中特异性过度表达 Sirt3，显示出对中风诱导的损伤的保护作用。从机制上讲，Sirt3 可以通过抑制缺血 (OGD) 后的缺氧诱导因子-1α (HIF-1α) 信号传导来调节血管内皮生长因子 (VEGF) 的表达。我们的研究结果表明，Sirt3 通过调节星形胶质细胞中的 HIF-1α/VEGF 信号传导在缺血性中风中发挥保护作用，并且在急性期逆转 Sirt3 表达可能是中风治疗的一个有价值的方向。