我们前期研究表明铅暴露上调神经元限制性沉默因子（NRSF）的表达，抑制突触囊泡相关蛋白的转录水平，导致其蛋白水平下降从而影响学习记忆。铅暴露如何影响NRSF表达导致学习记忆障碍，其机制不清楚。lncRNA在基因调控方面发挥着重要作用，预实验通过高通量测序并经qPCR技术发现在铅暴露模型中lncRNA-HN的表达明显升高，沉默lncRNA-HN后NRSF的表达显著下降。我们采用RNA结合蛋白免疫共沉淀技术显示lncRNA-HN与hnRNP-U有特异性的结合，并且在铅暴露模型中观察到hnRNP-U核转位。通过生物信息学分析hnRNP-U可与NRSF相互作用。故我们推测铅暴露可通过上调lncRNA-HN表达，促进hnRNP-U核转位，进而调控NRSF的表达。本项目将在整体和细胞水平深入研究lncRNA-HN在铅暴露影响学习记忆中的作用，为早期诊断和治疗铅暴露的神经毒性提供新的思路和理论基础。

Our previous study showed that lead exposure increased the expression of NRSF and inhibited the transcription level of synaptic vesicle associated protein, resulting in the decrease of its protein level, thereby affecting learning and memory. The mechanism of lead exposure affects the NRSF expression resulting in learning and memory disorder is unclear. lncRNA plays an important role in gene regulation. The high-throughput sequencing and quantitative real-time PCR (qPCR) technology showed that lncRNA-HN expression significantly increased in lead exposed model, and the expression of NRSF decreased significantly after lncRNA-HN silencing. We use RNA binding protein immunoprecipitation technique to show specific binding between lncRNA-HN and heterogeneous nuclear ribnucleoprotein U (hnRNP-U), and hnRNP-U nuclear translocation was observed in lead exposure model. Using bioinformatics analysis, we found that hnRNP-U interacts with neuron-restrictive silencer factor (NRSF). Therefore, we speculate that lead exposure increases the expression of lncRNA-HN and promotes the nuclear transposition of hnRNP-U, and then regulates the expression of NRSF. This project will study the role of lncRNA-HN in lead exposure on learning and memory at overall and cellular levels, and provide a new idea and theoretical basis for early diagnosis and treatment of neurotoxicity of lead exposure.