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异位主动脉弓移植小鼠模型

Mouse model of heterotopic aortic arch transplantation.

作者信息

Chereshnev Igor, Trogan Eugene, Omerhodzic Sabina, Itskovich Vitalii, Aguinaldo Juan-Gilberto, Fayad Zahi A, Fisher Edward A, Reis Ernane D

机构信息

Department of Medicine and the Zena and Michael Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.

出版信息

J Surg Res. 2003 May 15;111(2):171-6. doi: 10.1016/s0022-4804(03)00039-8.

DOI:10.1016/s0022-4804(03)00039-8
PMID:12850459
Abstract

BACKGROUND

Syngeneic heterotopic transplantation of segments of descending thoracic aortas containing atherosclerotic lesions from hypercholesterolemic mice into normocholesterolemic recipients has been useful for studies on plaque regression and stabilization. Because lesion development is more rapid and exuberant in the aortic arch, a technique of transplantation of the mouse aortic arch was developed.

MATERIALS AND METHODS

C57BL/6, apoE-deficient (apoE-/-) (hypercholesterolemic) mice were fed a Western diet for 22 weeks and used as donors of aortic-arch segments containing atherosclerotic lesions. Twenty syngeneic transplants were performed on age-matched wild-type (normocholesterolemic) mice. Aortic arches containing atherosclerotic lesions were implanted on the abdominal aorta of recipient mice by end-to-side microsurgical anastomosis. Two weeks after transplantation, grafts were noninvasively imaged in vivo by magnetic resonance (MR) microscopy. Grafts harvested four weeks after transplantation were submitted for histological examination.

RESULTS

All recipients survived the entire follow-up period (1 month) without complications. Duration of recipient procedure ranged from 90 to 120 (mean, 105) min; aortic clamping time varied from 45 to 60 min. In vivo MR microscopy demonstrated patency of the grafts and wall thickening that corresponded to the preexisting atherosclerotic lesions. Histology confirmed patency and atherosclerotic thickening of the grafts, and showed no evidence of acute tissue damage.

CONCLUSIONS

Syngeneic transplantation of the aortic arch in mice represents a useful alternative model for studies on morphology, imaging, and mechanisms of atherosclerosis. The curvature of the aortic arch is preserved after implantation onto the abdominal aorta, providing clear landmarks for noninvasive assessment using MR.

摘要

背景

将含有高胆固醇血症小鼠动脉粥样硬化病变的胸降主动脉节段同基因异位移植到正常胆固醇血症受体中,已被用于斑块消退和稳定的研究。由于主动脉弓处病变发展更快且更严重,因此开发了一种小鼠主动脉弓移植技术。

材料与方法

将C57BL/6载脂蛋白E缺陷(apoE-/-)(高胆固醇血症)小鼠喂食西式饮食22周,用作含有动脉粥样硬化病变的主动脉弓节段的供体。对年龄匹配的野生型(正常胆固醇血症)小鼠进行了20次同基因移植。通过端侧显微外科吻合术将含有动脉粥样硬化病变的主动脉弓植入受体小鼠的腹主动脉。移植后两周,通过磁共振(MR)显微镜对移植物进行体内无创成像。移植后四周收获的移植物进行组织学检查。

结果

所有受体在整个随访期(1个月)内存活,无并发症。受体手术持续时间为90至120(平均105)分钟;主动脉夹闭时间为45至60分钟。体内MR显微镜显示移植物通畅,且壁增厚与先前存在的动脉粥样硬化病变相符。组织学证实移植物通畅且有动脉粥样硬化增厚,未显示急性组织损伤的证据。

结论

小鼠主动脉弓同基因移植是一种用于动脉粥样硬化形态学、成像及机制研究的有用替代模型。将主动脉弓植入腹主动脉后,其曲率得以保留,为使用MR进行无创评估提供了清晰的标志。

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