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Therapeutic implication of MicroRNA-320a antagonist in attenuating blood clots formed during venous thrombosis
Journal of Thrombosis and Thrombolysis ( IF 4 ) Pub Date : 2024-02-23 , DOI: 10.1007/s11239-024-02947-6
Swati Srivastava , Iti Garg , Nilanjana Ghosh , Rajeev Varshney

Venous thrombosis (VT) is a complex multi-factorial disease and a major health concern worldwide. Its clinical implications include deep vein thrombosis (DVT) and pulmonary embolism (PE). VT pathogenesis involves intricate interplay of various coagulants and anti-coagulants. Growing evidences from epidemiological studies have shown that many non-coding microRNAs play significant regulatory role in VT pathogenesis by modulating expressions of large number of gene involved in blood coagulation. Present study aimed to investigate the effect of human micro RNA (hsa-miR)-320a antagonist on thrombus formation in VT. Surgery was performed on Sprague–Dawley (SD) rats, wherein the inferior vena cava (IVC) was ligated to introduce DVT. Animals were divided into four groups (n = 5 in each group); Sham controls (Sham), IVC ligated-DVT (DVT), IVC ligated-DVT + transfection reagent (DVT-NC) and IVC ligated-DVT + miR320a antagonist (DVT-miR-320a antagonist). IVC was dissected after 6 h and 24 h of surgery to estimate thrombus weight and coagulatory parameters such as levels of D-dimer, clotting time and bleeding time. Also, ELISA based biochemical assays were formed to assess toxicity of miRNA antagonist in animals. Our experimental analysis demonstrated that there was a marked reduction in size of thrombus in hsa-miR-320a antagonist treated animals, both at 6 h and 24 h. There was a marked reduction in D-dimer levels in hsa-miR-320a antagonist treated animals. Also, blood clotting time was delayed and bleeding time was increased significantly in hsa-miR-320a antagonist treated rats compared to the non-treated and Sham rats. There was no sign of toxicity in treated group compared to control animals. Hsa-miR-320a antagonist could be promising therapeutic target for management of VT.



中文翻译:

MicroRNA-320a 拮抗剂对减少静脉血栓形成过程中形成的血栓的治疗意义

静脉血栓形成(VT)是一种复杂的多因素疾病,也是全世界的主要健康问题。其临床意义包括深静脉血栓形成(DVT)和肺栓塞(PE)。VT 发病机制涉及各种凝血剂和抗凝血剂复杂的相互作用。越来越多的流行病学研究证据表明,许多非编码microRNA通过调节大量参与凝血的基因的表达,在VT发病机制中发挥着重要的调节作用。本研究旨在探讨人类微小RNA(hsa-miR)-320a拮抗剂对VT血栓形成的影响。对 Sprague-Dawley (SD) 大鼠进行手术,结扎下腔静脉 (IVC) 以引入 DVT。将动物分为四组(每组 n = 5);假手术对照(Sham)、IVC结扎-DVT(DVT)、IVC结扎-DVT+转染试剂(DVT-NC)和IVC结扎-DVT+miR320a拮抗剂(DVT-miR-320a拮抗剂)。手术后 6 小时和 24 小时解剖 IVC,以估计血栓重量和凝血参数,例如 D-二聚体水平、凝血时间和出血时间。此外,还形成了基于 ELISA 的生化测定法来评估 miRNA 拮抗剂在动物中的毒性。我们的实验分析表明,hsa-miR-320a 拮抗剂治疗的动物的血栓大小在 6 小时和 24 小时均显着减小。hsa-miR-320a 拮抗剂治疗的动物中 D-二聚体水平显着降低。此外,与未治疗的大鼠和假手术大鼠相比,hsa-miR-320a拮抗剂治疗的大鼠的凝血时间延迟,出血时间显着增加。与对照组动物相比,治疗组没有出现毒性迹象。Hsa-miR-320a 拮抗剂可能成为治疗 VT 的有希望的治疗靶点。

更新日期:2024-02-23
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