腔内药物输送到鼠标动静脉瘘内皮
Summary
After puncturing the aorta through the inferior vena cava (IVC) to create an aorto-caval fistula in the mouse, solution containing a drug is infused into the IVC via the same needle, followed by incubation. This method enables more robust drug delivery to the venous endothelium compared to the external route.
Abstract
治疗剂的递送，以提高动静脉瘘（AVF）成熟可以通过腔内或外部途径给药。简单的鼠AVF模型用的药物溶液至静脉内皮同时作为瘘创建腔内施用相结合。这个模型的技术问题进行了讨论。在全身麻醉下腹部切口由和主动脉和下腔静脉（IVC）被曝光。在肾下主动脉和下腔静脉解剖夹紧。近端和远端夹紧后，穿刺部位进行曝光，将25g针头被用来穿刺主动脉并进入下腔静脉两壁。穿刺后，立即报告基因表达的病毒载体在IVC通过相同的针注入，随后温育15分钟。相比由外部给药途径腔内给药方法使能更健壮的病毒基因递送到静脉内皮。这诺夫递送l的方法将有利于研究，探索在AVF成熟内皮的作用，并能在外科手术的时间腔内给药。
Introduction
鼠aortovenous瘘（AVF）的主动脉和下腔静脉（IVC）之间穿刺模型现在是一个既定的技术。1在该模型中，红外肾主动脉的两壁与地下25针被刺破，退出进毗邻肾下腔静脉;前主动脉入口孔被修复以简单的压缩，并且不需要缝合修复。串行随访检查采用高分辨率多普勒超声和病理分析表明，AVF有一个成熟阶段，再一个失败的阶段，扼要重述人类AVF的已知病理生理学2
探索了调节AVF成熟机制，需要用于输送治疗剂来熟化AVF内皮改进的方法。治疗剂递送至血管可以是通过血管内递送至内腔，或通过外部传递到外膜。外部递送的一个实例是玉米常用的聚醚凝胶的外膜应用。当加热到体温这种共聚物是热可逆的，并从液体到固体凝胶转化。当在体内局部施用药物在普卢兰尼克凝胶混合5,6-实现先前的研究已经表明持续的药物递送。3,4-病毒载体或siRNA与的Pluronic凝胶的外膜应用已报道是有效的血管周围递送系统，我们有还报告说，治疗由肽刺激外膜人外植隐静脉的导致内皮细胞受体蛋白的磷酸化。7
在另一方面，调查也同时使用病毒和非病毒载体腔内交付8-10犬和兔11,12车型静脉移植的。在这些报告中，静脉收获后进行基因转移体外 。伊斯拉米等报道的血管内的病毒基因递送y以颈动脉原位脉，而无需创建一个旁路13 Gloverman等。在大鼠股动脉，腹壁浅静脉瘘裸DNA的报道腔内和外膜交付14梅奥组报道在小鼠颈总动脉，颈内静脉瘘外膜的药物输送15,16然而，这些先前报告的模型需要缝合吻合创造在AVF。在这份报告中，腔内给药并同时创造AVF在小鼠中的描述，使用AVF创作的缝合线少的模型。通过使用本变形鼠AVF模型可以执行用于腔内药物输送到瘘管的静脉肢的简单方法。
Protocol
Representative Results
Discussion
鼠AVF模型的这种修改包含在AVF创建时腔内药物递送到静脉内皮。一个AVF通过穿刺用地下25针的红外肾主动脉和延伸穿过相对的主动脉壁进入下腔静脉穿刺，随后的药物溶液注射通过同一针创建。该解决方案是维持内静脉， 即 ，在AVF的静脉肢体，直到去夹紧。什么区别于其他鼠类AVF模型17-19这种模式是缺乏缝合或胶水可能导致管腔狭窄，急性血栓形成，并与分子分析可能的干扰。使?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
This work was supported in part by the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Program Merit Review Award I01-BX002336, the National Institute of Health grant R56-HL095498, as well as with the resources and the use of facilities at the VA Connecticut Healthcare System, West Haven, CT.
Materials
| Pluronic F-127 | Sigma-Aldrich | P2443-250G | Used as 30% solution in d-water |
| GFP antibody | NOVUS BIOLOGICALS INC | NB100-1770 | |
| Ad-CMV-GFP | VECTOR BIOLABS | 1060 | |
| 0.9% Sodium Chloride Irrigation, USP | Baxter | 2F7122 | |
| BD PrecisionGlide Needle 25G x 5/8 | BD | 305122 | |
| BD 1ml Syringe Tuberculin Slip Tip | BD | 309659 | |
| Scarpel | Surgical Design Inc | 22079707 | |
| 6-0 ETHILON P-1 11mm 3/8c Reverse Cutting | ETHICON INC | 697G | |
| Vevo 770 ultrasound machine | Visualsonics | 20-60 Mhz scan head; RMV-704 | |
| Vascular clamp | Roboz Surgical Instrument Co. | RS-5424 | |
| Clamp applying forceps | Roboz Surgical Instrument Co. | RS-5410 |
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