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应用多光子显微镜观察依诺肝素在激光诱导血管内皮损伤模型中的体内抗栓和溶栓疗效。

Visualization of in vivo thromboprophylactic and thrombolytic efficacy of enoxaparin in laser-induced vascular endothelial injury model using multiphoton microscopy.

机构信息

Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

出版信息

Am J Transl Res. 2015 Jan 15;7(1):79-87. eCollection 2015.

Abstract

Enoxaparin is used postoperatively for the prevention of venous thromboembolism. In vitro studies and clinical trials have demonstrated the anticoagulant and antithrombotic efficacy of enoxaparin. In this study, we visualised thromboprophylactic and thrombolytic efficacy of enoxaparin in a laser-induced thrombus formation model in vivo using two-photon laser-scanning microscopy (TPLSM). Thrombus was induced by the selective irradiation of vascular endothelium in arterioles of the cecum of green fluorescent protein transgenic mice. The thromboprophylactic and thrombolytic efficacy of enoxaparin was visualised in vivo real-time using TPLSM. Platelet adhesion, aggregation, and platelet-dependent thrombus formation were observed in the laser-induced thrombus formation model with reproducibility. Laser-induced thrombus formation was significantly inhibited by enoxaparin pretreatment as the thromboprophylactic agent, as compared with control. The mean thrombus volumes were 652 microcubic meters in mice pretreated with enoxaparin and 8906 microcubic meter in control mice. Enoxaparin reduced the volume of laser-induced thrombus when using it as a thrombolytic agent. The mean rate of reduction was 59 percent. In a lipopolysaccharide-induced sepsis model, thromboprophylactic efficacy of enoxaparin was also observed in vivo in real-time. In vivo thromboprophylactic and thrombolytic efficacy of enoxaparin can be visualised at the single platelet level in the laser-induced endothelium injury model using TPLSM.

摘要

依诺肝素术后用于预防静脉血栓栓塞。体外研究和临床试验已经证明了依诺肝素的抗凝和抗血栓形成作用。在这项研究中,我们使用双光子激光扫描显微镜(TPLSM)在体内激光诱导的血栓形成模型中观察到依诺肝素的血栓预防和溶栓效果。血栓通过对 GFP 转基因小鼠盲肠小动脉血管内皮的选择性照射诱导。使用 TPLSM 实时体内可视化依诺肝素的血栓预防和溶栓效果。在可重现的激光诱导的血栓形成模型中观察到血小板黏附、聚集和血小板依赖性血栓形成。依诺肝素作为预防剂预处理可显著抑制激光诱导的血栓形成,与对照组相比。依诺肝素预处理组的平均血栓体积为 652 立方微米,对照组为 8906 立方微米。当依诺肝素作为溶栓剂使用时,它减少了激光诱导的血栓体积。平均减少率为 59%。在脂多糖诱导的脓毒症模型中,也实时观察到依诺肝素的血栓预防作用。在 TPLSM 中,在激光诱导的内皮损伤模型中,可以在单个血小板水平上实时观察到依诺肝素的体内血栓预防和溶栓效果。

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