外泌体circHDAC9在OSAS认知功能障碍中的作用机制研究

阻塞性睡眠呼吸暂停（OSAS）是认知功能障碍的独立危险因素，circRNA通过竞争性结合miRNA参与认知功能障碍的发生。前期研究发现，miR-138上调和组蛋白去乙酰化酶(sirtuin 1)的表达，诱导海马神经元细胞衰老，促进阿尔茨海默病的发生。生物信息学预测circHDAC9与miR-138-5p互成碱基配对，而circRNA在外泌体中含量丰富，预实验结果提示，OSAS合并认知功能障碍患者血浆外泌体circHDAC9表达减少。因此我们猜想，OSAS下血浆外泌体传递的circHDAC9表达减少，导致miR-138-5p升高，衰老因子表达增加，引起海马神经元细胞衰老，导致认知功能障碍。本研究从临床标本、体外细胞及动物模型探讨外泌体circHDAC9通过miR-138-5p调控认知功能障碍的分子机制，为OSAS相关认知功能障碍的防治、诊断分子标志物的筛选提供新思路。

Obstructive sleep apnea (OSAS) is an independent risk factor for cognitive dysfunction, and circRNAs are involved in the occurrence of cognitive dysfunction through competitive binding of miRNAs. Previous studies have found that miR-138 up-regulates the expression of sirtuin 1, inducing senescence of hippocampal neurons and promotes the occurrence of Alzheimer's disease. Bioinformatics predicted that circHDAC9 was paired with miR-138-5p by mutual nucleotide, and circRNA is abundant in exosomes. The results of pre-experiment suggest that plasm exosomal circHDAC9 expression is decreased in patients of OSAS combined with cognitive dysfunction. Therefore, we hypothesized that the decreased expression of circHDAC9 transmitted by plasma exosomes under OSAS led to the increase of miR-138-5p which could lead to the senescence of hippocampal neurons and cognitive dysfunction by increasing the expression of senescence factors. In this study, the molecular mechanism of exosomal circHDAC9 in cognitive dysfunction by regulating miR-138-5p from clinical specimens, in vitro cell and animal models, providing a new idea for the prevention and treatment of OSAS-related cognitive dysfunction and the screening of molecular markers for diagnosis.