Sindeeva Olga A, Gusliakova Olga I, Prikhozhdenko Ekaterina S, Shushunova Natalia A, Sukhorukov Gleb B
Vladimir Zelman Center for Neurobiology and Brain Rehabilitation, Skolkovo Institute of Science and Technology, Moscow, Russia.
Science Medical Center, Saratov State University, Saratov, Russia.
Bio Protoc. 2024 Sep 20;14(18):e5070. doi: 10.21769/BioProtoc.5070.
Arterial delivery to the kidney offers significant potential for targeted accumulation and retention of cells, genetic material, and drugs, both in free and encapsulated forms, because the entire dose passes through the vessels feeding this organ during the first circulation of blood. At the same time, a detailed study on the safety and effectiveness of developed therapies in a large number of experimental animals is required. Small laboratory animals, especially mice, are the most sought-after in experimental and preclinical testing due to their cost-effectiveness. Most of the described manipulations in mice involve puncturing the walls of the abdominal aorta or renal artery for direct administration of solutions and suspensions. Such manipulations are temporary and, in some cases, result in long-term occlusion of the aorta. Ultimately, this can lead to disruption of blood flow as well as functional and morphological changes to the kidneys. In addition, few of these protocols describe targeted delivery to the kidney. The presented protocol involves the injection of test substances or suspensions through the renal artery into one of the kidneys. The catheter is implanted into the femoral artery and then advanced into the abdominal aorta and renal artery within the vessels. In this case, the integrity violation of the renal artery or abdominal aorta is absent. Occlusion of the renal artery is necessary only immediately at the time of injection to minimize the entry of the injected substance into the aorta. This protocol is similar to the clinical procedure for delivering a catheter into the renal artery and is designed for real-world operating conditions. Key features • The protocol involves implantation of a catheter into the vascular system through a puncture of the femoral artery, similar to the clinical procedure. • The catheter is moved inside the vessels without puncture or ligation to the aorta or renal artery. • The protocol involves only a short-term block of the blood supply to the target kidney (the time required for direct administration of the drug). • Suitable for chronic experiments on mice, since the catheter is removed from the vascular system immediately after drug administration.
通过动脉将细胞、遗传物质和药物(包括游离形式和封装形式)输送到肾脏具有显著的靶向积累和滞留潜力,因为在血液首次循环期间,整个剂量都会通过为该器官供血的血管。与此同时,需要对大量实验动物中已开发疗法的安全性和有效性进行详细研究。小型实验动物,尤其是小鼠,因其成本效益高,在实验和临床前测试中最受青睐。小鼠中描述的大多数操作都涉及穿刺腹主动脉或肾动脉壁以直接注射溶液和悬浮液。此类操作是临时性的,在某些情况下会导致主动脉长期闭塞。最终,这可能导致血流中断以及肾脏的功能和形态变化。此外,这些方案中很少描述对肾脏的靶向递送。所提出的方案涉及通过肾动脉将测试物质或悬浮液注射到一侧肾脏中。将导管植入股动脉,然后在血管内推进至腹主动脉和肾动脉。在这种情况下,不存在肾动脉或腹主动脉完整性受损的情况。仅在注射时立即阻断肾动脉,以尽量减少注射物质进入主动脉。该方案类似于将导管插入肾动脉的临床操作,是为实际操作条件设计的。关键特征 • 该方案涉及通过穿刺股动脉将导管植入血管系统,类似于临床操作。 • 导管在血管内移动,无需穿刺或结扎主动脉或肾动脉。 • 该方案仅涉及对目标肾脏的短期血液供应阻断(直接给药所需时间)。 • 适用于小鼠的慢性实验,因为给药后立即将导管从血管系统中取出。