视网膜色素上皮（RPE）自噬障碍介导的细胞慢性炎症与年龄相关性黄斑变性（AMD）发病密切相关。课题组既往研究发现氧化型低密度脂蛋白（OX-LDL）浓度增高引起RPE慢性炎症，及丹参单体有抗脂质氧化损伤效应。然而，自噬在AMD发病中的作用尚不完全明确，丹酚酸A是否具有保护作用及其机制不清。课题组拟通过体内外实验，揭示高脂活化mTOR-P62通路，抑制RPE细胞自噬，激活炎性因子，诱导AMD发生的设想；同时提出应用纳米包裹中药单体丹酚酸A,对AMD进行干预，观察其对mTOR-P62-自噬-炎症因子通路的调节。通过调控蛋白磷酸化、纳米-SiRNA及重组质粒等手段，探讨脂质氧化损伤中PI3K/Akt/mTOR调控P62/Keap1蛋白失衡介导ASC/NLRP3表达的分子机制，同时验证纳米颗粒-中药单体在治疗AMD中的有效性。上述成果将为AMD的病理研究和临床治疗开拓新的思路。

Recent years researchers found out that there is close relationship between early-phase AMD and chronic inflammation which is induced by rpe cells autophagy dysfunction.Our research group proved out in preliminary studies that high levels of OX-LDL in blood can leads to chronic inflammation in RPE layer, meanwhile salvia miltiorrhiza and its monomers have anti-oxidative functions.While the specific mechanism of autophagy in AMD pathology is still remained unclear. As a continuation of the previous work,we speculate that lipid peroxidation activate mTOR-P62 signal,depressing RPE cells autophagy and inducing RPE inflammation, and we plan to design nanoparticle-chinese medicine monomer to discuss AMD treatment and its modulation to mTOR-P62-autophagy-inflammation.By using phosphorylated proteins、nanopartivle-SiRNA and specific plasmids,we plan to study mechanism of modulation of PI3K/Akt/mTOR to P62/Keap1 and secondary ASC/NLRP3 expression,.Then verify availability of namoparticle component in curing AMD disease.This project is going to explore new pattern in studying pathology and pathogenesis of AMD and targets for therapy.