miR1298参与调控氧化应激反应在丙烯酰胺神经毒性中的分子机制

丙烯酰胺（AA）是广泛存在于环境和食品中的污染物，具有明确的神经毒性。研究显示氧化应激是其引发神经毒性的主要因素，但具体分子机制仍未被阐明。miRNAs是一类大量存在于生命体并参与绝大多数生命活动的非编码RNA，可调控氧化应激及其引起疾病的发生和发展。本团队从miRNA角度对AA毒性机制展开深入研究，发现AA在引起SD雌性大鼠出现神经毒性症状的同时，脑组织中miR1298的表达量也显著下调，该结果在细胞水平得到验证。据此，本课题拟解决地科学问题为：miR1298调控氧化应激对AA神经毒性的分子作用机制。通过确定miR1298调控的目标信号通路，预测并鉴定在该通路的靶基因及其调控途径，阐明其对氧化应激的调控作用，并在动物实验中加以验证，最终揭示miR1298调控AA神经毒性的分子机制。为全面解析AA神经毒性机制，寻找新的AA生物标志物和干预靶点提供理论依据，也为外源污染物的研究提供新思路。

AA is a neurotoxicin, which occur widely in environment and foods. The recent studies have demonstrated that oxidative stress response plays a key role in AA-induced neurological disorders, but the detailed molecular mechanism remains obscure. MicroRNAs (miRNAs) are small non-coding RNAs involved in almost vital movement, including the generation and development of diseases triggered by oxidative stress response. Our team carried out the research on AA toxicity mechanism based on miRNA analysis. In our previous study, AA induced neurotoxicity in SD female rats, and the expression level of miR1298 in brains of AA-induced SD rats reduced obviously through high-throughput sequencing and qRT-PCR. The same results were found in vivo. Hence, the key scientific issue of this project is the molecular mechanism of modulating oxidative stress by miR1298. We will definite the target pathway regulated by miR1298, predict and identify its target gene located in this pathway, and analyze their function. All the results will discover the molecular mechanism about oxidative stress modulated by miR1298. Moreover, the animal experiment will illuminate the functional mechanism of miR1298 involved in AA-induced neurotoxicity, which will provide the theoretical basis for clarifying the molecular mechanism of AA-induced neurotoxicity, seeking the target biomarker for AA exposure and AA toxicity intervention.