Department of Anesthesiology, Women's Health Center of Shanxi, Children's Hospital of Shanxi, Taiyuan, Shanxi, China.
Department of Critical Care Medicine, Chongqing Yubei District People's Hospital, Chongqing, 401120, China.
Cardiovasc Toxicol. 2024 Oct;24(10):1125-1138. doi: 10.1007/s12012-024-09903-z. Epub 2024 Jul 31.
The present study focused on exploring the clinical value and molecular mechanism of LncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in sepsis and sepsis-induced myocardial dysfunction (SIMD). 122 sepsis patients and 90 healthy were included. Sepsis patients were categorized into SIMD and non-MD. The expression levels of MCM3AP-AS1 and miRNA were examined using RT-qPCR. Diagnostic value of MCM3AP-AS1 in sepsis assessed by ROC curves. Logistic regression to explore risk factors influencing the occurrence of SIMD. Cardiomyocytes were induced by LPS to construct cell models in vitro. CCK-8, flow cytometry, and ELISA to analyze cell viability, apoptosis, and inflammation levels. Serum MCM3AP-AS1 was upregulated in patients with sepsis. The sensitivity and specificity of MCM3AP-AS1 were 75.41% and 93.33%, for recognizing sepsis from healthy controls. Additionally, elevated MCM3AP-AS1 is a risk factor for SIMD and can predict SIMD development. Compared with the LPS-induced cardiomyocytes, inhibition of MCM3AP-AS1 significantly attenuated LPS-induced apoptosis and inflammation; however, this attenuation was partially reversed by lowered miR-28-5p, but this reversal was partially eliminated by CASP2. MCM3AP-AS1 may be a novel diagnostic biomarker for sepsis and can predict the development of SIMD. MCM3AP-AS1 probably participated in SIMD progression by regulating cardiomyocyte inflammation and apoptosis through the target miR-28-5p/CASP2 axis.
本研究旨在探讨长链非编码 RNA MCM3AP 反义 RNA 1(MCM3AP-AS1)在脓毒症和脓毒症诱导的心肌功能障碍(SIMD)中的临床价值和分子机制。纳入 122 例脓毒症患者和 90 例健康对照者。将脓毒症患者分为 SIMD 组和非 SIMD 组。采用 RT-qPCR 检测 MCM3AP-AS1 和 miRNA 的表达水平。通过 ROC 曲线评估 MCM3AP-AS1 在脓毒症中的诊断价值。采用 logistic 回归分析影响 SIMD 发生的危险因素。用 LPS 诱导心肌细胞构建体外细胞模型。用 CCK-8、流式细胞术和 ELISA 分析细胞活力、凋亡和炎症水平。脓毒症患者血清中 MCM3AP-AS1 上调。MCM3AP-AS1 识别健康对照者和脓毒症患者的敏感性和特异性分别为 75.41%和 93.33%。此外,MCM3AP-AS1 升高是 SIMD 的危险因素,可预测 SIMD 的发展。与 LPS 诱导的心肌细胞相比,抑制 MCM3AP-AS1 显著减轻了 LPS 诱导的凋亡和炎症;然而,miR-28-5p 的降低部分逆转了这种抑制作用,但这种逆转部分被 CASP2 消除。MCM3AP-AS1 可能是脓毒症的一种新型诊断生物标志物,可预测 SIMD 的发展。MCM3AP-AS1 可能通过调节靶基因 miR-28-5p/CASP2 轴参与 SIMD 的进展,从而调节心肌细胞炎症和凋亡。