新生儿缺氧缺血性脑病（HIE）是发育期严重疾病，探索其损伤机制意义重大。我们前期在新生鼠缺氧缺血脑组织中筛选得到差异表达的长链非编码RNA(lncRNA)BC088414，发现其能调控细胞凋亡（已发表）。继而采用生物信息学分析,发现BC088414序列包含microRNA（miR-30d-5p等）结合位点，提示BC088414可能为特异microRNA的竞争性内源RNA（ceRNA）。进一步分析发现，miR-30d-5p靶基因包含Casp6等凋亡相关基因, 强烈提示BC088414可作为ceRNA削减microRNA对其靶基因的抑制，上调凋亡相关基因表达，促进神经元凋亡。为证实此设想，本课题将建立体内外缺氧缺血神经损伤模型，探讨BC088414对特异microRNA及其靶基因的调节机制，并对lncRNA调控策略用于减轻发育期脑损伤的效果进行评价，确定最佳治疗时间窗，为HIE治疗提供新思路。

Neonatal hypoxic-ischemic encephalopathy (HIE) is a serious neurological disease in children during developing period. It is very important to explore the injury and reparation mechanism of HIE. In the preliminary work, we have found that 322 long non-coding RNAs (lncRNAs) were differently expressed between hypoxic-ischemic (HI) and normal brain tissues screened by RNA chip. Among them BC088414 is the one with the maximum differential expression. Silencing of BC088414 in PC12 cell, a cell line derived from a pheochromocytoma of the rat adrenal medulla, decreased PC12 cell apoptosis, suggesting BC088414 participates in the regulation of cell apoptosis (these results have been published). When comparing the sequences of BC088414 and microRNAs through bioinformatics analysis, we found that the sequence of BC088414 contains the binding site of miR-30d-5p. Then we predicted the targeted genes of miR-30d-5p using Targetscan and microRNA.org database, it showed that some apoptosis related genes such as caspase 6 were targeted by miR-30d-5p. Therefore, we proposed that BC088414 might regulate HI induced neuronal apoptosis as the competing endogenous RNA (ceRNA) of microRNAs. We hypothesize that when BC088414 binds to microRNAs such as miR-30d-5p, the inhibition effect of miR-30d-5p on gene expression will be attenuated, consequently the expression of miR-30d-5p targeted genes such as caspase 6 will be up-regulated, followed by enhanced neuronal apoptosis and brain damage induced by HI. To prove this hypothesis, in the present study, we will first construct HI induced neuronal damage model in vitro and rat brain damage model in vivo. Then using these models, we’ll try to clarify the regulation effect of BC088414 on the microRNAs and targeted genes through ceRNA pathway, examine the effect of lncRNA regulating strategy on attenuating HI induced brain damage in neonatal rat, and explore the best therapeutic time window, finally provide new ideas for HIE therapy and prevention.