水飞蓟宾调控hnRNP-U对慢性铅暴露致学习记忆受损的影响及其机制研究

环境重金属铅具有很强的神经毒性，慢性铅暴露可导致儿童学习记忆损害。前期研究表明铅暴露可以促进hnRNP-U核转位上调NRSF表达进而抑制SV2C和HAP1表达，从而影响学习记忆。在铅暴露细胞模型中通过预实验筛选出一种具有神经保护作用的黄酮类化合物水飞蓟宾能明显下调hnRNP-U表达和核转位。研究发现水飞蓟宾可以通过调控NF-κB发挥神经保护作用，我们在铅暴露细胞模型中发现水飞蓟宾可以通过NF-κB下调hnRNP-U表达。水飞蓟宾可以抑制STAT3核转位，通过免疫共沉淀方法观察到STAT3与hnRNP-U特异性结合。故我们推测，水飞蓟宾可能通过抑制NF-κB下调hnRNP-U的表达，此外还可通过STAT3抑制hnRNP-U核转位，进而在铅暴露致学习记忆受损中起保护作用。本项目将在整体和细胞水平深入研究水飞蓟宾在铅暴露致学习记忆受损中的疗效和机制，为治疗铅暴露的神经毒性提供新的治疗和理论基础。

Lead, the environmental heavy metal, has neurotoxicity, and chronic lead exposure can impair children's learning and memory. Previous studies have shown that lead exposure can promote hnRNP-U nuclear translocation to up-regulate NRSF expression and thereby inhibit SV2C and HAP1 expression, affecting learning and memory. In the lead-exposed cell model, Silybin, a flavonoid, with neuroprotective effects was screened through pre-experiment, which can significantly down-regulate hnRNP-U expression and nuclear translocation. Studies have found that Silybin has neuroprotection by regulating NF-κB. We have found in a cell model of lead exposure that Silybin can down-regulate hnRNP-U expression through NF-κB. What`s more, Silybin can inhibit the nuclear translocation of STAT3, and the specific binding of STAT3 to hnRNP-U was observed by immunoprecipitation. Therefore, we speculate that Silybin may down-regulate the expression of hnRNP-U by acting on NF-κB. In addition, it may also inhibit the nuclear translocation of hnRNP-U through STAT3, and play a protective role in lead-induced learning and memory impairment. This project will deeply study the efficacy and mechanism of Silybin in learning and memory impairment caused by lead exposure at the overall and cellular level, and provide a new method and theoretical basis for the treatment of lead-induced neurotoxicity.