早产儿脑白质损伤（WMI）可致残及致死，探索WMI发病机制意义重大。我们前期研究发现，miR-466b-5p是WMI中抑制少突胶质细胞（OLs）分化的重要分子（已发表），但其作用机制尚不清楚。生物信息学分析发现，长链非编码RNA（lncRNA）Neat1序列中有miR-466b-5p的结合位点，髓鞘形成正调控基因Lpar1/Edg2是miR-466b-5p的靶基因。我们的前期结果发现Neat1过表达后会抑制miR-466b-5p和上调Lpar1/Edg2，提示Neat1可能作为miR-466b-5p的竞争性内源RNA（ceRNA），通过调节Lpar1/Edg2的表达进而调控OLs分化成熟。本课题拟通过建立细胞和动物实验模型，探讨Neat1/miR-466b-5p/Lpar1分子途径在OLs分化成熟中的作用，并探索靶向Neat1的策略治疗WMI的效果和最佳时间窗，为WMI治疗提供新思路。

White matter injury (WMI) in preterm neonates is associated with considerable mortality and morbidity. It is of great importance to explore the pathogenesis of WMI. Our previous study found that miR-466b-5p is an important molecule in WMI that inhibits oligodendrocytes (OLs) differentiation (published), but its regulatory mechanism is still unclear. Bioinformatics analysis found that the long non-coding RNA (lncRNA) Neat1 sequence has a binding site for miR-466b-5p, and the positive regulatory gene for myelination Lpar1/Edg2 is the target gene of miR-466b-5p. Our previous results revealed that overexpression of Neat1 will inhibit miR-466b-5p expression and upregulate Lpar1/Edg2, suggesting that Neat1 may act as competitive endogenous RNA (ceRNA) of miR-466b-5p, which regulates the expression of Lpar1/Edg2 and thus regulates OLs differentiation and maturation. This project intends to explore the role of Neat1/miR-466b-5p/Lpar1 in OLs differentiation and maturation by establishing in vitro and in vivo models, investigate the effect and the ideal time window of strategies targeting Neat1 on WMI improvement, and offer new perspectives on potential treatments for WMI.