Ferric Chloride-induced Murine Thrombosis Models.

Ferric Chloride-induced Murine Thrombosis Models.
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DOI:
10.3791/54479
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发表时间:
2016-09-05
期刊:
Journal of visualized experiments : JoVE
影响因子:
--
通讯作者:
Sen Gupta A
Sen Gupta A
中科院分区:
其他
文献类型:
--
作者:
Li W;Nieman M;Sen Gupta A

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动脉血栓形成(血凝块)是与慢性炎症相关的许多全身性疾病的常见并发症,包括动脉粥样硬化、糖尿病、肥胖、癌症和慢性自身免疫性风湿病。血栓是大多数心脏病发作、中风和肢体丧失的原因,使得血栓形成成为极其重要的公共卫生问题。由于这些血栓源于不适当的血小板活化和随后的凝血,因此治疗上靶向这些系统对于开发更安全的治疗方法具有重要的临床意义。由于止血系统的复杂性,体外实验无法复制血液与血管壁的相互作用;因此,体内研究对于了解血栓形成的病理机制至关重要。为此,已经在小鼠中开发了各种血栓形成模型。其中,氯化铁(FeCl 3)诱导的血管损伤是一种广泛使用的闭塞性血栓形成模型,其报告了无菌封闭血管系统中血小板的活化和聚集。该模型基于氧化还原诱导的内皮细胞损伤,该模型简单且对抗凝剂和抗血小板药物敏感。阻塞血流的血栓形成所需的时间给出了与血栓性疾病相关的血管损伤、血小板活化和聚集的定量测量。我们已经显著改进了这个FeCl 3诱导的血管血栓形成模型,这使得数据具有高度的可重复性和最小的变化。在这里,我们描述了该模型,并提出了代表性的数据,从几个实验装置,证明了该模型在血栓形成研究的效用。
Arterial thrombosis (blood clot) is a common complication of many systemic diseases associated with chronic inflammation, including atherosclerosis, diabetes, obesity, cancer and chronic autoimmune rheumatologic disorders. Thrombi are the cause of most heart attacks, strokes and extremity loss, making thrombosis an extremely important public health problem. Since these thrombi stem from inappropriate platelet activation and subsequent coagulation, targeting these systems therapeutically has important clinical significance for developing safer treatments. Due to the complexities of the hemostatic system, in vitro experiments cannot replicate the blood-to-vessel wall interactions; therefore, in vivo studies are critical to understand pathological mechanisms of thrombus formation. To this end, various thrombosis models have been developed in mice. Among them, ferric chloride (FeCl3) induced vascular injury is a widely used model of occlusive thrombosis that reports platelet activation and aggregation in the context of an aseptic closed vascular system. This model is based on redox-induced endothelial cell injury, which is simple and sensitive to both anticoagulant and anti-platelets drugs. The time required for the development of a thrombus that occludes blood flow gives a quantitative measure of vascular injury, platelet activation and aggregation that is relevant to thrombotic diseases. We have significantly refined this FeCl3-induced vascular thrombosis model, which makes the data highly reproducible with minimal variation. Here we describe the model and present representative data from several experimental set-ups that demonstrate the utility of this model in thrombosis research.
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发表时间: 2013
期刊: REDOX BIOLOGY
影响因子: 11.4
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期刊: Redox biology
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