■缺血性中风成为死亡和残疾的主要原因。它可以由于血管内或心脏血栓栓塞而发展。反映不同中风机制的动物模型仍在开发中。使用光化学血栓形成,我们根据血栓位置开发了一个可行的斑马鱼模型(脑内与心内)。我们使用实时成像和溶栓剂验证了该模型。
■我们使用转基因斑马鱼幼虫(flk:gfp),在内皮细胞中表达特异性荧光。我们注射了玫瑰红,光敏剂作为光敏剂的混合物,和荧光剂进入幼虫的主静脉。然后,我们通过暴露于共焦激光(560nm)并染色血流(RITC-葡聚糖)诱导血栓形成来评估体内实时血栓形成。我们通过检查组织纤溶酶原激活物(tPA)的活性来验证脑内和心内血栓形成模型。
■光化学药物诱导转基因斑马鱼脑内血栓形成。实时成像技术证实了血栓的形成。在体内模型中观察到血管内皮细胞的损伤和凋亡。通过使用光血栓形成的相同方法建立了心内血栓形成模型,并通过tPA溶栓对模型进行验证。
■我们开发并验证了两种容易获得的斑马鱼血栓模型,成本效益高,和直观的评估溶栓药物的疗效。这些模型可用于广泛的未来研究,如筛选和新的抗血栓药物的疗效评估。
UNASSIGNED: Ischemic stroke becomes a major cause of death and disability. It can develop due to intravascular or cardiac thromboemboli. Animal models that reflect diverse stroke mechanisms remain under development. Using photochemical thrombosis, we developed a feasible zebrafish model according to the thrombus location (intracerebral vs. intracardiac). We validated the model using real-time imaging and thrombolytic agent.
UNASSIGNED: We used transgenic zebrafish larvae (flk:gfp), which express specific fluorescence in endothelial cells. We injected Rose Bengal, a photosensitizer as a mixture of photosensitizer, and a fluorescent agent into the cardinal vein of the larvae. We then evaluated real-time thrombosis in vivo by inducing thrombosis through exposure to a confocal laser (560 nm) and staining the blood flow (RITC-dextran). We validated intracerebral and intracardiac thrombotic models with checking the activity of tissue plasminogen activator (tPA).
UNASSIGNED: The photochemical agent induced the formation of intracerebral thrombi in transgenic zebrafish. Real-time imaging techniques confirmed the formation of the thrombi. The damage and apoptosis of the vessel\'s endothelial cells were seen in the in vivo model. An intracardiac thrombosis model was developed by the same method using photothrombosis, and the model was validated through thrombolysis by tPA.
UNASSIGNED: We developed and validated two zebrafish thrombosis models that are readily available, cost-effective, and intuitive for assessing the efficacy of thrombolytic agents. These models can be used for a broad spectrum of future studies, such as screening and efficacy assessment of new antithrombotic agents.