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首页> 外文期刊>Thrombosis and Haemostasis: Journal of the International Society on Thrombosis and Haemostasis >The mouse dorsal skinfold chamber as a model for the study of thrombolysis by intravital microscopy
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The mouse dorsal skinfold chamber as a model for the study of thrombolysis by intravital microscopy

机译：小鼠背部皮褶腔作为通过活体显微镜研究溶栓的模型

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Although intravital microscopy models of thrombosis in mice have contributed to dissect the mechanisms of thrombus formation and stability, they have not been well adapted to study long-term evolution of oc-clusive thrombi. Here, we assessed the suitability of the dorsal skinfold chamber (DSC) for the study of thrombolysis and testing of thrombolytic agents by intravital microscopy. We show that induction of FeCl 3-induced occlusive thrombosis is achievable in microvessels of DSCs, and that thrombi formed in DSCs can be visualised by intravital microscopy using brightfield transmitted light, or fluorescent staining of thrombus components such as fibrinogen, platelets, leukocytes, and von Willebrand factor. Direct application of control saline or recombinant tissue-plasminogen activator (rtPA) to FeCl 3-produced thrombi in DSCs did not affect thrombus size or induce recanalisation. However, in the presence of hirudin, rtPA treatment caused a rapid dose-dependent lysis of occlusive thrombi, resulting in recanalisation within 1 hour after treatment. Skin haemorrhage originating from vessels located inside and outside the FeCl 3-injured area was also observed in DSCs of rtPA-treated mice. We further show that rtPA-induced thrombolysis was enhanced in plasminogen activator inhibitor-1-deficient (PAI-1-/-) mice, and dropped considerably as the time between occlusion and treatment application increased. Together, our results show that by allowing visualization and measurement of thrombus lysis and potential bleeding complications of thrombolytic treatments, the DSC provides a model for studying endogenous fibrinolysis and for first-line screening of thrombolytic agents. Furthermore, using this system, we found that thrombin and clot aging impair the thrombolytic action of rtPA towards FeCl 3-produced thrombi.
机译：尽管小鼠体内血栓形成的显微​​镜检查模型有助于剖析血栓形成和稳定性的机制，但它们并未很好地适应研究闭塞性血栓的长期演变。在这里，我们评估了背部皮褶腔室（DSC）用于溶栓研究和通过活体显微镜检测溶栓剂的适用性。我们表明，FeCl 3诱导的闭塞性血栓形成在DSCs的微血管中是可以实现的，并且在DSCs中形成的血栓可以通过活体显微镜使用明场透射光或血栓成分（如纤维蛋白原，血小板，白血球和von Willebrand因子。直接将对照盐水或重组组织纤溶酶原激活剂（rtPA）应用于DSC中由FeCl 3产生的血栓不会影响血栓的大小或引起再通。但是，在水rud素存在下，rtPA治疗引起闭塞性血栓的剂量依赖性快速溶解，导致在治疗后1小时内再通管。在rtPA处理的小鼠的DSC中也观察到源自位于FeCl 3损伤区域内部和外部的血管的皮肤出血。我们进一步显示，rtPA诱导的溶栓作用在纤溶酶原激活物抑制剂1缺陷型（PAI-1-/-）小鼠中得到增强，并且随着阻塞和治疗应用之间的时间增加而显着下降。总之，我们的结果表明，通过允许可视化和测量血栓溶解和溶栓治疗的潜在出血并发症，DSC提供了一个模型，用于研究内源性纤维蛋白溶解和一线筛选溶栓剂。此外，使用该系统，我们发现凝血酶和凝块老化会损害rtPA对FeCl 3产生的血栓的溶栓作用。

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