基于lncRNA-MALAT1调控血管内皮功能探讨益气养血通络法预防DR的作用机制

“早期治络”是课题组预防糖尿病血管并发症的原创性理论，干预DR已有多年临床积累。最新研究发现，高糖状态下氧化应激加剧，激活lncRNA-MALAT1/-p38MAPK-MMP-9/VEGF通路，损伤血管内皮功能，在DR发生中起重要作用。课题组前期研究表明，在DR发生前预防性给予络通方，可明显延缓糖尿病大鼠DR的发生，减轻氧自由基损伤、改善血管内皮功能。由此，我们推测络通方可能通过减轻氧化应激，调控lncRNA-MALAT1表达及DNA甲基化修饰，达到保护血管内皮功能，延缓DR发生。本课题以MALAT1为切入点，拟采用活体荧光成像、生物信息学等技术，体内外实验相结合，研究不同病程DR特点、信号通路相关因子的表达及其内在相关性，探讨益气活血通络法预防DR的作用机制，为从表观遗传学机制上寻找突破口，实现中医药预防DR提供了新的思路和方法，为中医治未病理论指导下建立糖尿病早期预防策略提供科学依据。

"Dredging collaterals in early treatment" is our original theory in preventing diabetic vascular complications, which has been applied in treating diabetic retinopathy (DR) for years. A New study has revealed that hyperglycemia can provoke severe oxidative stress and activate lncRNA-MALAT1/-p38MAPK-MMP-9/VEG pathway, which leads to impairment of endothelial cell function, playing an important role in the onset of DR. Previous studies of our research group have shown that preventive treatment by Luo Tong formula before the onset of DR can alleviate or delay the process of DR in diabetic rats. Luo Tong formula can also ameliorate oxygen free radical injury and improve endothelial cell function. Alleviating oxidative stress, reversing the expression of lncRNA-MALAT1 and DNA methylation to protect endothelial cell function is probably the mechanism. Our study is focus on studying on the mechanism of DR protection by the principle of tonifying Qi, nourishing blood and dredging collaterals in vivo and vitro studies of diabetic rats. The study is targeted at MALAT1 using fluorescence imaging, bioformatics to study the characteristics of DR in different course, expression of signaling pathway factors and their relations. We aimed at providing new targets and ideas for TCM treatment and prevention of DR, and trying to elucidate the significance of disease prevention and preventive treatment in TCM.