化疗引起的血管毒性 - 实时<em>在体内</em>船舶减值成像
Summary
We herein describe the method of fibered confocal fluorescent microscopy (FCFM) based imaging, which provides an innovative mode to understand physiological phenomena at the cellular and sub-cellular levels in animal subjects.
Abstract
化学疗法的某些类可能施加急性血管变化，可能进展成长期条件可能会使病人血管并发症的风险增加。然而，尽管所述安装临床证据，有血管毒性，因此，血管/心血管病症一组异质性的病因的明确研究的缺乏尚待阐明。此外，该可依据血管毒性的机制可以完全由化疗引起的心脏毒性，这是直接细胞损伤相关的原理不同。我们建立了实时， 体内分子成像平台以评价抗癌疗法的潜在急性血管毒性。
我们已经建立了体内 ，小鼠的高分辨率分子成像，一个平台适用于密闭机关和参照一个BLO内血管可视化而每个单独的同一个体内外径船只充当其自身的控制。阿霉素给药后的血管壁均受损，代表血管毒性的一个独特的机制，可能是在终末器官损伤的早期事件。在此，纤维状共聚焦荧光显微镜（FCFM）基于成像的方法进行说明，它提供了一个创新的方式来了解生理现象在细胞和亚细胞水平的动物受试者。
Introduction
临床证据表明，几类化疗引起的各种由雷诺现象，高血压，心肌梗死，脑血管攻击，肝静脉occlusivedisease 1,2体现血管病症。 “'意外'抗血管生成药物”是一个相当新的名词，它描述了传统的化疗药物是作为可能的血管生成抑制剂，虽然他们不是最初开发用于这一目的3-5，但设计的征收尽可能少的消除肿瘤细胞的“抵押品损害“正常细胞尽可能3。几种化疗已经暗示为血管 – 毒物在应用血清生物标记物的临床研究中观察到。在这些被烷化剂（如环磷酰胺），铂化合物（例如顺铂）和蒽环类1,2,5-7。
急性心脑血管并发症，可能会出现一个resul吨血管毒性化疗所致的。他们可能会进步到像动脉粥样硬化，占后期血管发病的危险性增加慢性疾病。然而，尽管安装的临床证据，有指定的研究强调血管毒性的机制的缺乏，因此，它们造成的确切发病机理的进一步澄清是必要的。
在揭示化疗引起的血管毒性机制的一个主要挑战来源于体内调查血管功能的复杂性。我们描述了本文中的高清晰度的体内分子成像的小鼠，使捕捉血流和血管'特性的一个平台。这个平台便于直接治疗性血管效应的检测：实时，以及跟随它们过了一段时间的同一个体中。
Protocol
Representative Results
Discussion
评价化疗诱导的血管毒性是具有挑战性，因为在可视化血管的动态响应于实时一个刺激的难度。大量临床研究已经牵连的几个化疗造成直接损伤血管，但这种毒性的机制和特点仍有待澄清。我们建立了实时， 体内分子成像的平台如本文8-10描述评价化疗在含有纤维状共聚焦荧光显微镜的小鼠的潜在血管毒性。这种高解析度的分子的小鼠成像是适合用于可视化动脉血流和血管'架构?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
None
Materials
| Name of Material/ Equipment | Company | Catalog Number | Comments/Description |
| general anesthesia (100mg/kg ketaset and 6mg/kg XYL-M2). | Fort Dodge Animal Health, IA, USA and Biove Laboratories, France | ||
| a depilatory cream (Veet) | ReckittBenckiser, Bristol, UK | ||
| A 30-gauge, 1/2-inch needle attached to 1 ml syringe | |||
| FITC dextran at a volume of 100 µl (10 mg/ml; FD2000S, MW 2000000 Dalton) | Sigma | ||
| Doxorubicin (8 mg/kg, Adriamycin) | Teva, Israel | ||
| paclitaxel (1.2 mg/kg, Medexel) | Taro, Israel | ||
| Saline |
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