血清 miR-499a-5p 对脓毒症心肌功能障碍的预测价值及其调控机制。
Predictive value and regulatory mechanism of serum miR-499a-5p on myocardial dysfunction in sepsis.
机构信息
Department of Critical Care Medicine, The Second Hospital of Shandong University, No. 247 Beiyuan Dajie Street, Jinan City, 250012, Shandong Province, China.
出版信息
J Cardiothorac Surg. 2021 Oct 15;16(1):301. doi: 10.1186/s13019-021-01679-5.
BACKGROUND
This study sought to investigate the predictive value and regulatory mechanism of serum miR-499a-5p in sepsis-induced myocardial dysfunction (SIMD).
METHODS
A total of 60 patients with sepsis and 60 healthy volunteers were enrolled in this study. The serum levels of miRNAs (miR-451, miR-378 and miR-499a-5p) were detected. Receiver operating characteristic curve and logistic regression analysis were used to evaluate the diagnostic and prognostic value of miR-499a-5p in SIMD patients. AC16 cells were used to establish SIMD model in vitro using lipopolysaccharide (LPS). An analysis was conducted for miR-499a-5p expression, cell viability, and the concentration of creatine kinase-MB isoform (CK-MB), brain natriuretic peptide (BNP), superoxide dismutase (SOD) and cytochrome C oxidase IV (COX IV). The downstream target of miR-499a-5p was verified.
RESULTS
Our results revealed a poor expression of miR-499a-5p in the serum of SIMD patients, while no significant difference was evident for miR-451 and miR-378. The level of miR-499a-5p in the survival group was higher than the non-survival group. miR-499a-5p elicited good diagnostic and prognostic value for SIMD. Our findings revealed that miR-499a-5p was decreased significantly in LPS-treated cardiomyocytes. After overexpression of miR-499a-5p, the cell viability increased, and the concentrations of CK-MB and BNP were decreased, while the concentrations of SOD and COX IV were increased. EIF4E was validated as the target of miR-499a-5p. After overexpression of EIF4E, the cell viability was decreased and the concentrations of CK-MB and BNP were increased while the concentrations of SOD and COX IV were decreased.
CONCLUSION
The level of miR-499a-5p is weak in SIMD patients. miR-499a-5p has a good diagnostic and prognostic value for SIMD by inhibiting EIF4E transcription.
背景
本研究旨在探讨血清 miR-499a-5p 在脓毒症诱导的心肌功能障碍（SIMD）中的预测价值和调控机制。
方法
本研究纳入了 60 例脓毒症患者和 60 名健康志愿者。检测了 miRNA（miR-451、miR-378 和 miR-499a-5p）的血清水平。采用受试者工作特征曲线和 logistic 回归分析评估 miR-499a-5p 在 SIMD 患者中的诊断和预后价值。体外使用脂多糖（LPS）建立 SIMD 模型，使用 AC16 细胞。分析 miR-499a-5p 表达、细胞活力以及肌酸激酶同工酶-MB 同工酶（CK-MB）、脑利钠肽（BNP）、超氧化物歧化酶（SOD）和细胞色素 C 氧化酶 IV（COX IV）的浓度。验证了 miR-499a-5p 的下游靶标。
结果
我们的研究结果表明，SIMD 患者血清中 miR-499a-5p 的表达水平较低，而 miR-451 和 miR-378 则无明显差异。存活组的 miR-499a-5p 水平高于非存活组。miR-499a-5p 对 SIMD 具有良好的诊断和预后价值。我们的研究发现，LPS 处理的心肌细胞中 miR-499a-5p 的表达明显降低。过表达 miR-499a-5p 后，细胞活力增加，CK-MB 和 BNP 的浓度降低，而 SOD 和 COX IV 的浓度升高。EIF4E 被验证为 miR-499a-5p 的靶标。过表达 EIF4E 后，细胞活力降低，CK-MB 和 BNP 的浓度升高，而 SOD 和 COX IV 的浓度降低。
结论
SIMD 患者的 miR-499a-5p 水平较低。miR-499a-5p 通过抑制 EIF4E 转录对 SIMD 具有良好的诊断和预后价值。
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