BackgroundDiabetic cardiomyopathy (DCM) represents a major cause of heart failure and a large medical burden worldwide. This study screened the potentially regulatory targets of DCM and analyzed their roles in high glucose (HG)‐induced cardiomyocyte injury.MethodsThrough GEO database, we obtained rat DCM expression chips and screened differentially expressed genes. Rat cardiomyocytes (H9C2) were induced with HG. 3‐hydroxy‐3‐methylglutarylcoenzyme A synthase 2 (Hmgcs2) and microRNA (miR)‐363‐5p expression patterns in cells were measured by real‐time quantitative polymerase chain reaction or Western blot assay, with the dual‐luciferase assay to analyze their binding relationship. Then, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assay, lactate dehydrogenase assay, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme‐linked immunosorbent assay, and various assay kits were applied to evaluate cell viability, cytotoxicity, apoptosis, inflammation responses, and oxidative burden.ResultsHmgcs2 was the vital hub gene in DCM. Hmgcs2 was upregulated in HG‐induced cardiomyocytes. Hmgcs2 downregulation increased cell viability, decreased TUNEL‐positive cell number, reduced HG‐induced inflammation and oxidative stress. miR‐363‐5p is the upstream miRNA of Hmgcs2. miR‐363‐5p overexpression attenuated HG‐induced cell injury.ConclusionsHmgcs2 had the most critical regulatory role in DCM. We for the first time reported that miR‐363‐5p inhibited Hmgcs2 expression, thereby alleviating HG‐induced cardiomyocyte injury.

中文翻译：

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Hmgcs2是糖尿病心肌病的核心基因，受Hmgcs2负调控，促进高糖诱导的心肌细胞损伤

背景糖尿病心肌病（DCM）是心力衰竭的主要原因，也是全世界巨大的医疗负担。本研究筛选DCM的潜在调控靶点并分析其在高糖（HG）诱导的心肌细胞损伤中的作用。方法通过GEO数据库获取大鼠DCM表达芯片并筛选差异表达基因。用 HG 诱导大鼠心肌细胞 (H9C2)。通过实时定量聚合酶链反应或蛋白质印迹法测量细胞中 3-羟基-3-甲基戊二酰辅酶 A 合酶 2 (Hmgcs2) 和 microRNA (miR)-363-5p 的表达模式，并用双荧光素酶法分析它们的表达模式。绑定关系。然后，3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴化物测定、乳酸脱氢酶测定、末端脱氧核苷酸转移酶dUTP缺口末端标记测定、酶联免疫吸附测定和应用各种检测试剂盒评估细胞活力、细胞毒性、细胞凋亡、炎症反应和氧化负荷。结果Hmgcs2是DCM的重要枢纽基因。Hmgcs2 在 HG 诱导的心肌细胞中表达上调。Hmgcs2 下调增加了细胞活力，减少了 TUNEL 阳性细胞数量，减少了 HG 诱导的炎症和氧化应激。miR-363-5p 是 Hmgcs2 的上游 miRNA。miR-363-5p 过表达可减轻 HG 诱导的细胞损伤。结论 Hmgcs2 在 DCM 中具有最关键的调节作用。我们首次报道miR-363-5p抑制Hmgcs2表达，从而减轻HG诱导的心肌细胞损伤。