缺血性脑卒中（IS）是成年人致残的主要原因之一，目前尚无有效的药物治疗手段。最新研究表明，IS后神经元不仅发生凋亡与坏死，还可发生自噬，但其在IS后神经功能障碍中的作用尚存在争议。我们的前期研究发现，在神经元损伤模型中使用自噬激动剂可减少神经元死亡；而一类线粒体去乙酰化酶Sirt3在神经元损伤后表达增高，过表达Sirt3可激活线粒体自噬相关的Pink1-Parkin信号通路，发挥神经保护作用。结合文献报道，我们认为Sirt3在IS后的表达增加可能是一种内源性保护机制，可能通过调控线粒体自噬影响IS后神经元转归。本课题拟在以往工作基础上，利用基因表达干预技术，研究Sirt3及线粒体自噬在脑缺血再灌注损伤中的作用，明确Sirt3调控神经元线粒体自噬的分子机制，阐明IS后神经元线粒体自噬相关的分子机理与重要信号通路，为IS后脑保护研究提供新的思路。

Ischemic stroke (IS) is still one of the most common causes of long-term disability in adulthood, and drug treatment in clinical practice is limited. Recent studies demonstrated that besides apoptosis and necrosis, neuronal autophagy was also observed after IS, but its exact role in IS-induced neurological dysfunction was controversial. Our previous data showed that autophagy agonists could reduce neuronal death in vitro; the expression of Sirt3, a mitochondrial NAD+ -dependent protein deacetylase, was increased after IS, and overexpression of Sirt3 inhibits neuronal injury through regulating mitophagy associated Pink1-Parkin pathway. Together with recent studies, these results indicate that the increased expression of Sirt3 after IS might be an endogenous protective mechanism, which might influence neuronal outcome after IS through regulating mitophagy. On the basis of previous studies, the roles of Sirt3 and mitophagy in cerebral ischemia and reperfusion injury and the molecular mechanisms underlying Sirt3 in regulating neuronal mitophagy will be studied by using lentivirus-mediated overexpression and downregulation technology. It is possible to clarify the molecular network and important signaling of mitophagy after IS and to provide a theoretical basis for neuroprotective research.