miR-2467-3p/ABLIM1 轴通过调节炎症和氧化应激介导深静脉血栓的形成和发展

Yu Qiu, Meiying Yang, Xinting Che, Xinming Yu, Kangkang Zhi
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摘要

深静脉血栓(DVT)是骨科手术常见的术后并发症,发病机制复杂。本研究评估了 miR-2467-3p/ 作用结合 LIM 蛋白 1(ABLIM1)轴对血栓形成和人血管内皮细胞(HUVECs)进展的影响,旨在找出深静脉血栓形成的新型潜在生物标志物。通过下腔静脉狭窄建立了深静脉血栓大鼠模型。通过 PCR 分析了 miR-2467-3p/ABLIM1 轴的表达。用氧化低密度脂蛋白(ox-LDL)诱导 HUVEC。细胞计数试剂盒 8(CCK8)和 Transwell 试验评估了细胞的生长和运动。炎症和氧化应激通过促炎细胞因子以及 MDA 和活性氧(ROS)的生成进行评估。ABLIM1 在深静脉血栓大鼠中下调。过表达 ABLIM1 可抑制血栓形成,缓解炎症和氧化应激。在 HUVECs 中,ox-LDL 诱导 miR-2467-3p 明显增加,而 ABLIM1 则下降,miR-2467-3p 能负向调节 ABLIM1。敲除 miR-2467-3p 可以缓解 ox-LDL 对细胞生长和运动的抑制,并减轻炎症和氧化应激。而沉默则能逆转 miR-2467-3p 对 ox-LDL 诱导的 HUVECs 的影响。miR-2467-3p/ABLIM1轴通过调节HUVECs炎症和氧化应激调控深静脉血栓的发生和发展。
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miR-2467-3p/ABLIM1 Axis Mediates the Formation and Progression of Deep Vein Thrombosis by Regulating Inflammation and Oxidative Stress
Deep vein thrombosis (DVT) is a common postoperative complication of orthopaedic surgery with a complex pathogenesis mechanism. The effect of the miR-2467-3p/acting-binding LIM protein 1 (ABLIM1) axis on thrombus formation and human vascular endothelial cells (HUVECs) progression was evaluated aiming to identify a novel potential biomarker of DVT. DVT rat models were established by inferior vena cava stenosis. The expression of the miR-2467-3p/ABLIM1 axis was analyzed by PCR. HUVECs were induced with oxidative low-density lipoprotein (ox-LDL). Cell growth and motility were assessed by cell counting kit 8 (CCK8) and Transwell assay. The inflammation and oxidative stress were estimated by proinflammatory cytokines and generation of MDA and reactive oxygen species (ROS). ABLIM1 was downregulated in DVT rats. Overexpressing ABLIM1 could suppress the formation of thrombosis and alleviate inflammation and oxidative stress. In HUVECs, ox-LDL induced significantly increased miR-2467-3p and decreased ABLIM1, and miR-2467-3p could negatively regulate ABLIM1. The knockdown of miR-2467-3p could alleviate the inhibited cell growth and motility by ox-LDL, and the inflammation and oxidative stress were also attenuated. While silencing could reverse the effect of miR-2467-3p on ox-LDL-induced HUVECs. The miR-2467-3p/ABLIM1 axis regulates the occurrence and development of DVT through modulating HUVECs inflammation and oxidative stress.
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