内皮细胞主要以糖酵解供能，产生的乳酸通过单羧酸转运体4（MCT4）转出细胞。前期研究证实MCT4的下调参与糖尿病内皮损伤的发生，但MCT4的调控机制不明。miR-425与糖代谢关系密切，预实验提示Slc16a3（编码MCT4）是miR-425的靶基因，活化的NF-κB可上调miR-425。故提出假说：糖尿病时，活化的NF-κB入核，上调miR-425，靶向Slc16a3，抑制MCT4的表达，使乳酸在胞内积聚，导致内皮损伤。本项目拟在人脐静脉内皮细胞上采用miR-425模拟物和反义核酸干预，探讨miR-425对MCT4表达的影响；通过双荧光素酶报告基因法验证Slc16a3是miR-425的靶基因，NF-κB可与miR-425启动子区结合促进其转录；建立miR-425敲除小鼠糖尿病模型，探究miR-425在糖尿病内皮损伤中的作用。从而在细胞及整体水平上论证假说，为糖尿病内皮损伤的防治提供新思路

Endothelial cells rely primarily on glycolysis, and lactic acid is transferred out of cells via the monocarboxylate transporter 4 (MCT4). Our previous study showed that the down-regulation of MCT4 is involved in diabetic endothelial injury, but the regulation mechanism of MCT4 is unclear. Previous studies showed that miR-425 correlates closely with glucose metabolism. Pre-experiment suggests that Slc16a3, which coding MCT4, is a potential target gene of miR-425. The activated NF-κB up-regulates miR-425. So we hypothesized that the activated NF-κB transferred into the nucleus, promoting the expression of miR-425, and targeting Slc16a3 to inhibit MCT4 expression, resulting in lactic acid accumulation, leading to endothelial injury in diabetes. We will use human umbilical vein endothelial cells transfected with miR-425 mimics or antisense nucleic acid to study the effects of miR-425 on MCT4 expression. Then we will validate that Slc16a3 is the target gene of miR-425 and the activated NF-κB combines with the promoter of miR-425 through luciferase assay. Finally, we will establish miR-425 knockout diabetic mice model to study the effects of miR-425 on diabetic endothelial injury. Thus, our study will demonstrate the hypothesis in vitro and in vivo, providing a new intervention target for the prevention and treatment of diabetic endothelial injury.