Department of Cardiac Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, China.
Department of Cardiovascular Medicine, People's Hospital of Ningxia Hui Autonomous Region, The First Clinical College of Northwest University for Nationalities, Yinchuan, Ningxia Hui Autonomous Region 750002, China.
Mediators Inflamm. 2023 Jan 10;2023:9380398. doi: 10.1155/2023/9380398. eCollection 2023.
Myocardial ischemia-reperfusion (IR) injury is the restoration of blood flow post ischemia, which threatens the human life. Long noncoding RNA distal-less homeobox 6 antisense 1 (DLX6-AS1) has been found to take part in the IR-induced cerebral injury. Here, we determined the functional role of DLX6-AS1 in IR-induced myocardial injury. We ligated the left anterior descending coronary artery of rats to induce IR injury. IR injury rats exhibited severe tissue damage and increase of infraction size. The levels of lactate dehydrogenase (LDH), creatine kinase (CK), proinflammatory factors including MCP-1, IL-6, and IL-1, and cell apoptosis were also enhanced in IR rats, indicating that IR induced significant myocardial injury in rats. DLX6-AS1 expression was elevated in the myocardial tissues of IR injury rats, while DLX6-AS1 deficiency alleviated IR-induced myocardial injury in rats by reducing inflammatory response and cell apoptosis. Moreover, rat embryonic cardiomyocyte cell line H9c2 was subjected to hypoxia reoxygenation (HR). DLX6-AS1 was upregulated in the HR-treated H9c2 cells, and DLX6-AS1 enhanced the expression of F-box and WD40 repeat domain-containing 7 (FBXW7) by sponging miR-204-5p. Inhibition of DLX6-AS1 inhibited inflammatory response and cell apoptosis in H9c2 cells via miR-204-5p/FBXW7 axis. In conclusion, this work demonstrates that DLX6-AS1 accelerates myocardial IR injury through regulating miR-204-5p/FBXW7 axis. Thus, this work provides a novel ceRNA DLX6-AS1/miR-204-5p/FBXW7 axis in myocardial IR injury, and DLX6-AS1 may be a potential target for the treatment of myocardial IR injury.
心肌缺血再灌注（IR）损伤是缺血后血流的恢复，这威胁着人类的生命。长链非编码 RNA 远端同源盒 6 反义 1（DLX6-AS1）已被发现参与 IR 诱导的脑损伤。在这里，我们确定了 DLX6-AS1 在 IR 诱导的心肌损伤中的功能作用。我们结扎大鼠的左前降支冠状动脉诱导 IR 损伤。IR 损伤大鼠表现出严重的组织损伤和梗死面积增大。IR 大鼠的乳酸脱氢酶（LDH）、肌酸激酶（CK）、促炎因子包括单核细胞趋化蛋白-1（MCP-1）、白细胞介素-6（IL-6）和白细胞介素-1（IL-1）以及细胞凋亡水平也升高，表明 IR 诱导大鼠发生明显的心肌损伤。IR 损伤大鼠心肌组织中 DLX6-AS1 表达升高，而 DLX6-AS1 缺乏通过减轻炎症反应和细胞凋亡减轻 IR 诱导的大鼠心肌损伤。此外，大鼠胚胎心肌细胞系 H9c2 进行缺氧复氧（HR）处理。HR 处理的 H9c2 细胞中 DLX6-AS1 上调，DLX6-AS1 通过海绵 miR-204-5p 增强 F 框和 WD40 重复结构域 7（FBXW7）的表达。DLX6-AS1 抑制抑制了 H9c2 细胞中的炎症反应和细胞凋亡。总之，这项工作表明，DLX6-AS1 通过调节 miR-204-5p/FBXW7 轴加速心肌 IR 损伤。因此，这项工作为心肌 IR 损伤提供了一个新的 ceRNA DLX6-AS1/miR-204-5p/FBXW7 轴，DLX6-AS1 可能是治疗心肌 IR 损伤的潜在靶点。
