新生儿缺氧缺血性脑病（HIE）是重大难治性疾病，探索其损伤与修复机制十分必要。研究表明，坏死性凋亡是缺氧缺血(HI)后神经元死亡的重要原因，而受体相互作用蛋白3（RIP3）是调控坏死性凋亡的关键分子。我们既往研究发现RIP3在神经元HI后表达增加，并诱导坏死性凋亡发生。但是，对RIP3表达的调控机制不清楚。前期工作中，我们用芯片筛查发现新生鼠HI后脑组织非编码RNA差异表达明显。经生物信息学分析发现，这些差异表达的非编码RNA中含有多个靶向RIP3的长链非编码RNA（如ENSMUST00000127908）和微小RNA（如miR-223）。因此，我们推测靶向RIP3的非编码RNA在调控神经细胞坏死性凋亡中起着十分重要的作用。本课题将建立脑缺氧缺血体内及体外模型，探索调控神经元坏死性凋亡的核心非编码RNA，阐明非编码RNA之间及其与RIP3之间的调控机制，为临床治疗新生儿HIE提供新思路。

Neonatal hypoxic-ischemic encephalopathy (HIE) is a severe disease of nervous system. It is very important to explore the damage and reparation mechanism of HIE. Necroptosis has been found to participate in pathogenesis of many diseases, and the upregulation of receptor-interacting protein 3 (RIP3) is crucial to initiate the process of necroptosis. In the preliminary work, we have proved that RIP3 is up-regulated significantly in neurons with hypoxia-ischemia insult and mediates neuronal necroptosis. However, the regulatory mechanism for RIP3 expression is unclear. We predicted non-coding RNAs targeted to RIP3 through bio-informatics, and found that some of them such as ENSMUST00000127908 and miR-223 overlapped with the non-coding RNAs differently expressed between hypoxic-ischemic and normal brain tissues screened by RNA chip, suggesting that the variation of some specific non-coding RNAs is the crucial mechanism to regulate necroptosis in hypoxic-ischemic brain. In the present study, we’ll construct the in vivo and in vitro model to mimic HIE in newborn mice, select and identify critical non-coding RNAs targeted to RIP3, evaluate the regulating mechanisms among these non-coding RNAs and between non-coding RNAs and RIP3, thus provide new ideal for HIE therapy.