最近研究证实降糖处理并不能有效减轻心肌损伤，其原因可能与糖尿病介导的“代谢记忆”损伤密切相关，是连接糖代谢紊乱与心脏并发症的重要机制。我们采用表达谱基因芯片及分子生物学方法研究发现：即使给予降糖处理，高糖诱导的LncRNA-KCNQ1OT1与组蛋白去甲基化酶KDM3A表达上调持续进展，并伴随miR-128持续下调。此外，生物信息学数据库预测提示：KCNQ1OT1可能作为ceRNA通过miR-128靶向调控KDM3A，但其在糖尿病心肌“代谢记忆”损伤中的作用方式及调控机制均未见报道。本研究在阐明糖尿病心肌“代谢记忆”损伤具体表现的基础上，拟观察过表达或沉默KCNQ1OT1对糖尿病心肌“代谢记忆”损伤的影响，并探索“KCNQ1OT1/miR-128/KDM3A信号轴”在其中的的作用机制，从而为糖尿病心肌“代谢记忆”损伤的防治提供新的实验依据及干预靶点。

Recent studies have verified that glucose control could not effectively reduce myocardial damage, which is associated with diabetes-mediated ‘metabolic memory (MM)’ injury and constitutes important pathogenesis for cardiac complication. According to gene expression profile and molecular biological analysis, we find that LncRNA-KCNQ1OT1 and histone demethylase KDM3A are persistently up-regulated in myocardial MM injury in parallel with the constant down-regulation of miR-128. Furthermore, bioinformatic databases predicate that KCNQ1OT1 may act as a competing endogenous RNA, by which it sponges miR-128 and represses KDM3A expression. However, it is not clear whether KCNQ1OT1-drived alternations of miR-128 and KDM3A participates in myocardial MM injury. In the present study, (1) we attempt to observe the phenotypes and metabolic memory of cardiomyocytes in response to high glucose followed by hyperglycemic termination; (2) detect the effects of KCNQ1OT1 overexpression or silencing on the development of myocardial MM injury; (3) explore the underlying molecular mechanisms in association with KCNQ1OT1-mediated miR-128/KDM3A signaling pathway. This research may provide prospective targets and therapeutic strategies for the treatment of diabetic myocardial damage.