miR-302a通过硫氧还蛋白结合蛋白-2对肝脂代谢调控作用的研究

脂代谢异常发病率逐渐上升，危害人类健康，但分子机制尚未明确。硫氧还蛋白结合蛋白-2（TBP-2）是氧化还原调节蛋白，具有多种生物活性，并在脂代谢中起重要作用，其缺失可引起高脂血症、肝脂肪变性等脂代谢紊乱。miRNAs通过转录后调节作用调控蛋白表达，并与脂代谢密切相关。本项目选择TBP-2及生物信息学预测相关的miR-302a为研究对象，通过前期实验证实抑制HepG2细胞中miR-302a可增加TBP-2蛋白表达。本项目将在脂肪变性肝细胞模型和高脂小鼠模型中研究miR-302a、TBP-2及一些脂代谢相关基因表达变化；靶基因验证实验验证miR-302a对TBP-2作用位点；在正常肝细胞、小鼠体内和脂肪变性肝细胞模型、高脂小鼠模型分别过表达/抑制miR-302a，研究其对TBP-2的负调控作用及其对肝脂代谢的调控作用。该项目为脂代谢调控机制提供一定理论支持，具有实际应用价值。

Morbidity of lipid metabolism disorder is rising and harm to human health. Its molecular mechansim is still unclear. The thioredoxin binding protein-2 (TBP-2) is a redox regulating protein, which has various functions. TBP-2 plays an important role in lipid metabolism, and its deficiency results in lipid metabolism disorder such as hyperlipidemia and hepatic steatosis. miRNAs inhibit protein expression by gene posttranscription regulating, which is closely correlated with lipid metabolism disorder. This subject will take TBP-2 and predicted miR-302a as study targets,and our prevoius work showed knocked down miR-302a could increase the protein expression of TBP-2 in HepG2. So we will study the changes of expression on miR-302a,TBP-2 and some lipid metabolism related molecules in hepatic steatosis cell model and high-fat diet fed mice model. Then, we determine the target site by which miR-302a taregt on TBP-2. We will decrease or increase the expression of miR-302a in HepG2, normal mice, hepatic steatosis cell model and high-fat diet fed mice model to stduy the regulation roles of miR-302a on TBP-2 and lipid metabolism through TBP-2. This study could provide theory evidence on lipid metabolism regulatory mechanism and had the actual application value.