circPDK1靶向miR-30a-5p的“海绵”作用在糖尿病性白内障发生过程中对氧化应激和自噬的网络调控研究

晶状体上皮细胞（LECs）中的氧化应激反应和自噬活动失调参与了白内障的发病过程。课题组前期研究发现：糖尿病性白内障LECs中miR-30a-5p表达下降，可负性调控靶基因TP53INP1增强氧化应激反应，也可负性调控靶基因BECN1增强自噬活动；在持续性高糖状态下，LECs的氧化应激和自噬呈现动态变化并相互影响。为进一步了解miR-30a-5p的上游调控机制以及下游氧化应激和自噬二者相互之间的调控机制，本课题拟利用糖尿病小鼠动物模型，基于对环状RNA-circPDK1的表达干预，探讨其对miR-30a-5p的“海绵”作用，以及氧化应激和自噬活动之间相互影响的分子机制，完善上下游的网络调控关系，为糖尿病性白内障的防治提供新的干预靶点。

Oxidative stress and autophagy activity in lens epithelial cells (LECs) are involved in the pathogenesis of cataracts. Our previous study found that the expression of miR-30a-5p was decreased in LECs of diabetic cataracts. As a result of decreased expression of miR-30a-5p, the target gene TP53INP1 was negatively regulated to enhance oxidative stress; the target gene BECN1 was also negatively regulated to enhance autophagy; on the other hand, oxidative stress and autophagy of LECs show dynamic fluctuation and interaction in the persistent high glucose states . In order to understand the upstream regulatory mechanism of miR-30a-5p and the regulatory mechanism between oxidative stress and autophagy, our study intend to use the diabetic mouse model to probe into the “sponge” effect of miR-30a-5p and the molecular mechanism of interaction between oxidative stress and autophagy activity based on intervening into the expression of circRNA-circPDK1. Our study aims to provide new targets of intervention for the prevention and treatment of diabetic cataract.