婴幼儿在手术中长时间使用全身麻醉时，后者对发育期大脑的影响是临床医生关注的焦点。研究指出，长时间或反复的全身麻醉暴露，导致婴幼儿在青春期的认知功能损害发生率高于非暴露婴幼儿。我们的研究发现，七氟烷抑制神经干细胞向神经元分化，LncRNA-RIKEN以及下游通路在其中起了重要的调控作用，前期研究还提示，七氟烷暴露可以通过发育期大脑的损伤，进一步影响神经突触发育，导致远期认知功能障碍。因此，我们提出假说：七氟烷下调发育期大脑的LncRNA-RIKEN表达水平，竞争性影响miR-466i-3p的水平，导致靶基因BDNF的表达下调，进而抑制神经干细胞后续分化，导致远期学习和记忆能力损伤。并应用神经干细胞分化体系，以及条件性敲低或过表达RIKEN小鼠模型来开展项目工作。本项目的研究结果将为揭示全身麻醉影响婴幼儿神经与突触功能发育的机制，以及全身麻醉药物的改造提供表观遗传学角度的调控靶点和理论依据。

Infants and young children need long-term use of general anesthesia drugs during surgery, and the latter's long-term effects on the developmental brain are the focus of clinical attention. Studies suggest that prolonged or repeated exposure of infants and young children to general anesthesia can lead to cognitive impairment during puberty. Our study found that sevoflurane inhibits the differentiation of neural stem cells into neurons, LncRNA-RIKEN and downstream pathways play an important regulatory role. Previous studies have also suggested that sevoflurane exposure can further affect Neurite triggers, leading to long-term cognitive dysfunction through brain damage in developmental stages.Therefore, we hypothesized that sevoflurane down-regulates the expression level of LncRNA-RIKEN in the developmental brain, competitively affects the level of miR-466i-3p, leading to down-regulation of the target gene BDNF, thereby inhibiting the subsequent differentiation of neural stem cells, leading to long-term learning and memory impairment. The neural stem cell differentiation system and the conditional knockdown or overexpression of the RIKEN mouse model were used to carry out the project work. The research results of this project will provide an epigenetic point of regulation and theoretical basis for revealing the mechanism of general anesthesia affecting the development of nervous and synaptic function in infants and young children, as well as the transformation of general anesthetic drugs.