LncRNATP73-AS靶向miR-154-5p调控自噬在缺氧缺血性脑病发病机制中的作用

自噬与缺氧缺血脑损伤 (HIBD) 密切相关。抑制自噬可阻止新生大鼠HIBD诱导的海马锥体神经元细胞的死亡，我们前期芯片筛选发现新生SD大鼠HIBD后海马神经元内LncRNATP73-AS表达明显升高。生物信息学预测LncRNATP73-AS包含一个miR-154-5p的结合位点，ATG7是miR-154-5p靶基因之一，ATG7是自噬的一个重要标志基因。因此我们推测LncRNATP73-AS通过靶向miR-154-5p调控自噬可能是缺氧缺血脑损伤的新机制。本研究拟探讨：① 大鼠HIBD后LncRNATP73-AS，miR-154-5p，ATG7的表达变化；②LncRNATP73-AS和miR-154-5p在缺氧缺血性神经损伤中的作用;③LncRNATP73-AS对miR-154-5p和自噬调控的机制研究，该机制尚未见报道，具有源头创新性，为HIBD防治提供新靶标。

Autophagy is closely related to hypoxic-ischemic brain damage (HIBD) . Inhibition of autophagy in HIBD in newborn rats can prevent death of hippocampal pyramidal neuronal cells. Our high-throughput screening data indicated that the expression of LncRNATP73-AS was significantly increased in hippocampal neurons in HIBD. Bioinformatics analysis predicted its LncRNATP73-AS contains a binding site for miR-154-5p, its downstream target as the ATG7 gene, ATG7 is an important marker of autophagy. We hypothesized that LncRNATP73-AS regulated autophagy and brain injury by targeting miR-154-5p after HIBD. This study was to investigate that ①the changes of LncRNATP73-AS, miR-154-5p and ATG7 gene expression after HIBD;② The role of LncRNATP73-AS and miR-154-5p on neuronal survival after HIBD;③the mechanism of miR-154-5p and autophagy regulation by LncRNATP73-AS.Our study therefore provides new potential therapeutic target for HIBD.