内皮微颗粒LncRNA OIP5-AS1作为ceRNA调控NLPR3介导的糖尿病内皮功能障碍的机制研究

内皮功能紊乱是糖尿病血管病变的始动环节。前期我们发表文章报道，NLRP3炎症小体活化介导高糖诱导的内皮细胞损伤，但上游调控机制尚未阐明。课题组前期发现内皮微颗粒（EMPs）作为载体携带长链非编码RNA（LncRNA）参与糖尿病血管内皮损伤，芯片分析发现糖尿病EMPs中LncRNA OIP5-AS1显著升高，内皮细胞miR-7低表达，伴NLRP3活化及内皮功能损伤；生物信息学预测miR-7有相同MRE元件与OIP5-AS1及ELAVL1基因结合。因此，我们提出“EMPs携带OIP5-AS1作为miR-7的竞争性内源RNA，靶向调控ELAVL1/NLRP3通路介导糖尿病血管内皮损伤”的假设，构建LncRNA、miRNA、靶基因和炎症微环境间的调控网络，阐明EMPs携带OIP5-AS1调控ELAVL1表达参与NLRP3炎症小体介导的糖尿病内皮损伤的分子机制，为糖尿病内皮功能障碍的防治提供新靶点。

Endothelial dysfunction is the initial link of diabetic vascular disease. We previously reported that activation of NLRP3 inflammasome mediates the hyperglycemia induced endothelial cell injury, but the upstream regulatory mechanism has not been elucidated. We have identified that endothelial microparticles (EMPs), serve as a carrier carrying long non-coding RNA (LncRNA), participate in diabetes endothelial damage, chip analysis found that diabetic EMPs LncRNA OIP5-AS1 increased significantly, with miR-7 low expressed in endothelial cell, NLRP3 activation and endothelial dysfunction; bioinformatics analysis predicted that mir-7 had the same MRE components combined with OIP5-AS1 and ELAVL1 genes. Based on this, we hypothesized “LncRNA OIP5-AS1-containing EMPs serve as competitive endogenous RNA of miR-7, mediated diabetes vascular endothelial damage via targeting ELAVL1/NLRP3 inflammasome pathways”, building regulation network of LncRNA, miRNAs, target genes and inflammatory microenvironment, to clarify the molecular mechanism of OIP5-AS1-containing EMPs regulate NLRP3 inflammasome mediated diabetes endothelial dysfunction by targeting ELAVL1 expression, providing new interventions targets for the prevention and treatment of diabetes endothelial dysfunction.