组蛋白乙酰化修饰在锰致神经系统氧化应激损伤中的调控机制及姜黄素的干预研究

锰中毒致神经毒性机制不明，迄今未有特效治疗方法，是众多学者高度关注的重大公共卫生问题。锰可通过氧化应激损伤诱导神经毒性，但具体机制尚不明确。新近研究推测，组蛋白乙酰化修饰可能通过调控抗氧化物质的转录表达参与锰的神经毒性。本项目在课题组前期研究的基础上，从人群、动物和细胞三个层次，采用酶联免疫吸附实验（ELISA）、实时荧光定量PCR（qRT-PCR）、免疫印迹(Western Blotting)、定量染色质免疫沉淀（ChIP-qPCR）、四源磁共振、标准量化表测评等技术手段，同时siRNA转染及具有抗氧化活性的姜黄素干预处理不同体系研究对象，较深入系统地从组蛋白乙酰化修饰调控角度探讨锰致神经系统氧化应激损伤的分子机制，为锰中毒神经毒性的机制研究及预治提供新思路和科学依据。

The unclear mechanism of neurotoxicity caused by manganese poisoning and absence of specific therapeutic methods are major public health issues of great concern to many scholars. Manganese is able to induce neurotoxicity through oxidative stress injury, but the specific mechanism is still unclear. Recent studies have speculated that histone acetylation modification may be involved in the neurotoxicity of manganese by regulating the transcriptional expression of antioxidants. Based on the previous research ideas of the research group, this project will be conducted from the three levels of population, animal and cell by technical means of enzyme-linked immunosorbent assay (ELISA), real-time fluorescent quantitative PCR (qRT-PCR), western blotting (WB), quantitative chromatin immunoprecipitation (ChIP-qPCR), four-source magnetic resonance, standard quantitative table evaluation and others, meanwhile, siRNA transfection and curcumin with antioxidant activity will used to interfere with different levels of research subjects, so as to explore the molecular mechanism of oxidative stress damage induced by manganese in the nervous system deeply and systematically from the perspective of histone acetylation modification, which provided new ideas and scientific basis for the study on the mechanism and treatment of neurotoxicity of manganese poisoning.