miR-375-3p 调控Rasd1基因介导缺氧缺血性脑损伤后昼夜节律紊乱的新机制

缺氧缺血性脑损伤(HIBD)患儿常遗留昼夜节律紊乱，严重影响患儿生存质量。我们前期芯片筛选发现:HIBD 后大鼠松果体中miR-375-3p表达明显升高。生物信息学预测其下游靶基因之一是 Rasd1基因。而我们同时发现：HIBD后大鼠松果体中Rasd1基因表达显著降低。OGD模型中Rasd1与种基因家族表达趋势一致。Rasd1是依赖昼夜节律性的新型钟基因，因此我们设想： 松果体中miR-375-3p 对Rasd1 的调控可能是导致HIBD后节律紊乱的新机制。本研究拟探讨：①大鼠HIBD后松果体中miR-375-3p与Rasd1钟基因表达水平与昼夜节律的变化； ②miR-375-3p 过表达/表达沉默对原代松果体细胞的影响；③大鼠体内模型研究miR-375-3p对松果体Rasd1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。

Hypoxic-ischemic brain damage (HIBD) survivals often suffer from circadian rhythm disorders, which substantially affect their life qualities.Our.high-throughput screening data indicated that miR-375-3p,a microRNA, is significantly upregulated in rat pineal gland after HIBD. Bioinformatics analysis predictedits downstream target as the Rasd1 gene, the expression of Rasd1 is consistent with the clock family genes in OGD model.Rasd1 is a novel dependent circadian clock gene. We hypothesized that the impairment of the Rasd1 gene expression mediated by miR-375-3p led to the disorder of circadian disorder.To test this, we will first measure changes of miR-375-3p and Rasd1 gene expression after HIBD. We will then test the effects on pineal function when miR-375-3p is overexpressed or silenced. We will also study the relationships between miR-375-3p, Rasd1 gene and pineal function after HIBD. Our study therefore provides new potential therapeutic target..for circadian disorders after HIBD.