新生儿脑室内出血（IVH）造成的围产期脑损伤可遗留严重的神经系统后遗症，目前临床上尚无十分有效的治疗手段。最近研究表明小胶质细胞极化介导的神经炎症反应可能是围产期脑损伤的关键致病环节，但具体机制尚不清楚。我们在前期研究中发现线粒体去乙酰化酶SIRT3低表达可促进小胶质细胞M1型极化，抑制M2型极化，且下调SIRT3加剧了IVH后氧化应激反应与脑积水程度，提示SIRT3可能通过影响线粒体代谢调控小胶质细胞极化。在前期研究基础上，本课题组拟应用靶向抑制、RNA干扰与基因过表达技术调控SIRT3表达，在新生鼠IVH模型及离体培养小胶质细胞中，研究SIRT3调控M1/M2型小胶质细胞极化在新生儿IVH后脑损伤中的神经保护作用，可能的信号转导机制及关键效应分子。开展本项目研究不仅为小胶质细胞分化与功能研究提供新的调控机制与干预策略，更有望为新生儿IVH后脑损伤提供非常具有临床应用价值的治疗新靶点。

Neonatal intraventricular hemorrhage (IVH) can cause perinatal brain injury with severe neurological sequelae. Recent studies demonstrated that neuroninflammation mediated by microglial polarization may be the key pathogenesis of perinatal brain injury, but the the specific mechanisms are not yet clear. In our previous study, we found that low expression of the mitochondrial deacetylase SIRT3 can promote M1 and inhibit M2 microglial phenotype polarization. After IVH, down regulation of SIRT3 increases oxidative stress and causes hydrocephalus, suggesting that SIRT3 may regulate microglial polarization by affect the mitochondrial metabolism. In this research proposal, we plan to utilize inhibitor, RNA interference and gene overexpression techniques to manipulate the protective effect of SIRT3 via M1/M2 microglial polarization both in neonatal IVH rat models and in isolated microglial cells from them. We also plan to explore the potential signaling pathway as well as the key regulators. Completion of this study would not only provide new potential mechanisms for microglial differentiation and functionality, but also provides a novel therapeutic target for brain injury after neonatal IVH.