PPARγ调控脂滴相关蛋白caveolin-2影响口腔上皮异常增生的作用及机制研究

口腔潜在恶性疾病（OPMDs）具有发生上皮异常增生的潜能，明确上皮异常增生的调控机制对预防口腔癌具有重大意义。脂滴作为脂质中心在细胞上皮-间充质转化（EMT）中起着重要作用。基于申请人的前期研究结果及文献总结，本课题的假说为过氧化物酶体增殖物激活受体γ（PPARγ）通过调控与脂滴功能相关的窖蛋白-2（caveolin-2），影响脂肪酸由脂滴向线粒体运输、氧化，调控口腔上皮细胞异常增生。为验证该假说，本项目以脂滴为切入点，验证脂滴相关分子表达及其与口腔上皮异常增生的关系，明确其临床意义；探索PPARγ通过调控caveolin-2干预脂滴向线粒体输送脂肪酸的机制及对口腔上皮异常增生的影响；构建人工脂滴，评估其作为纳米载体治疗OPMDs的稳定性、有效性及安全性。本课题不仅有助于阐明脂滴调控的脂代谢重塑与口腔上皮异常增生的关系，明确相关分子机制，还可为OPMDs的防治提供重要思路与依据。

Oral potentially malignant disorders (OPMDs) have the risk of epithelial dysplasia. It is of great significance to clarify the regulatory mechanism of epithelial dysplasia for the prevention of oral cancer. Lipid droplets, as lipid center, play an important role in epithelial to mesenchymal transition (EMT). Based on our previous research and literature review on OPMDs, the hypothesis of this project is that peroxisome proliferator activated receptor gamma (PPARγ) affects the transport of fatty acid to mitochondria and fatty acid oxidation by regulating caveolin-2 expression, which is related to lipid droplet function, and thus regulates the oral epithelial dysplasia. In order to verify this hypothesis, this research takes lipid droplets as the breakthrough point to verify the expression of lipid droplet related molecules and its relationship with oral epithelial dysplasia, and clarify its clinical significance; explore the mechanism of PPARγ intervening lipid droplets to transport fatty acids to mitochondria by regulating caveolin-2; clarify the effect of lipid droplets' functional changes on fatty acid β-oxidation and oral epithelial dysplasia; construct artificial lipid droplets, and evaluate its stability, efficacy and safety as nano carriers for the treatment of oral epithelial dysplasia. This research not only helps to clarify the molecular mechanism and the relationship between oral epithelial dysplasia and lipid metabolism remodeling regulated by lipid droplets, but also provides new strategies and basis for the prevention and treatment of OPMDs.