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碳纳米管介导的基因沉默对急性心肌梗死后早期心肌细胞凋亡及心功能的影响。

Effects of carbon nanotube-mediated gene silencing on cardiomyocyte apoptosis and cardiac function during early acute myocardial infarction.

机构信息

Department of Cardiology, The Third Medical Center, Chinese PLA General Hospital, Beijing, People's Republic of China.

出版信息

Nanoscale. 2020 Nov 5;12(42):21599-21604. doi: 10.1039/d0nr05032f.

Abstract

RNA interference (RNAi) technology can achieve efficient and specific silencing of Caspase3 gene expression, thus providing new options for anti-apoptosis treatment. However, delivering siRNA to specific cells and tissues in the body is a significant challenge. Therefore, we aim to construct a functionalized single-walled carbon nanotube (F-CNT) bound to siRNA from Caspase3. The obtained gene transfer carrier F-CNT-siCas3 not only demonstrated a good water solubility and biocompatibility, but also had a high transfection efficiency of up to 82%, which significantly downregulated the expression level of the Caspase3 gene miRNA and protein in primary cardiomyocytes. Furthermore, it was verified by in vivo experiments that Caspase3 gene silencing had obvious protective effects on myocardial cell apoptosis, ventricular remodeling, and cardiac function in Sprague-Dawley (SD) rats after coronary artery ligation. This study may provide an important theoretical basis for the application of F-CNT in vivo siRNA gene therapy to treat cardiovascular diseases.

摘要

RNA 干扰 (RNAi) 技术可实现 Caspase3 基因表达的高效、特异性沉默,为抗细胞凋亡治疗提供了新选择。然而,将 siRNA 递送到体内的特定细胞和组织是一个重大挑战。因此,我们旨在构建一种功能性单壁碳纳米管 (F-CNT) 与 Caspase3 的 siRNA 结合。所得基因转载体 F-CNT-siCas3 不仅表现出良好的水溶性和生物相容性,而且转染效率高达 82%,显著下调了原代心肌细胞中 Caspase3 基因 miRNA 和蛋白质的表达水平。此外,体内实验验证了 Caspase3 基因沉默对冠状动脉结扎后 Sprague-Dawley (SD) 大鼠心肌细胞凋亡、心室重构和心功能具有明显的保护作用。该研究为 F-CNT 在体内 siRNA 基因治疗治疗心血管疾病中的应用提供了重要的理论依据。

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