Lopinavir/r治疗HIV时会出现老化性心血管并发症，这与我们前期研究发现该药物诱导血管内皮细胞老化有关。我们发现在Lopinavir/r诱导内皮细胞老化的同时，lncTUG1表达下调；TUG1在老龄小鼠血管组织及老化内皮细胞中表达下降；过表达TUG1可延缓内皮细胞老化进程，这提示TUG1可能与Lopinavir/r诱导内皮细胞老化有关。我们研究初步确定Creb/Myc参与调节TUG1的转录，并运用生物信息学手段找到TUG1下游靶蛋白MKRN1。由此我们推测Lopinavir/r导致血管内皮细胞老化的机制可能是通过Creb、Myc下调lncTUG1表达，影响其与MKRN1结合，继而作用于下游p53/p21、hTERT，最终导致了内皮细胞老化发生。本项目在前期研究基础上提出科学假说，探索lncTUG1在Lopinavir/r诱导内皮细胞老化中可能起到的重要作用及其作用分子机制。

Complications of aging vessels often occur during the treatment of anti-HIV drug, Lopinavir/r, which inhibits reverse transcriptional virus protease. This phenomenon might have relationship with endothelial cells senescence which induced by Lopinavir/r. Our initiating study shows lncTUG1 expression reduces in the Lopinavir/r induced senescent endothelial cells, nature senescent endothelial cells and vascular tissue of aging mice. Inhibition/over-expression of lncTUG1 leads to a/an accelerated/slow aging process. These results indicate lncTUG1 might play a vital role in Lopinavir/r induced endothelial cells senescence. Then, through bioinformatics methods, we found out the transcriptional factors Creb and Myc, which modulate the transcription of lncTUG1, as well as its downstream protein MKRN1. Therefore, our hypothesis is Lopinavir/r reduced expression of lncTUG1 through Creb and Myc, which influences the combination of TUG1 and MKRN1, then triggers the downstream signal molecular (p53/p21 or/and hTERT) to induce vascular endothelial cell senescence as the result. This study will explore the function of lncTUG1 in the process of Lopinavir/r induced endothelial cell senescence and the inner mechanism, for the purpose of providing a novel therapeutic method in diseases of anti-HIV drug induced aging related cardiovascular diseases.