Sun H, Valdivia L A, Subbotin V, Aitouche A, Fung J J, Starzl T E, Rao A S
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, PA 15213, USA.
Microsurgery. 1998;18(6):368-71. doi: 10.1002/(sici)1098-2752(1998)18:6<368::aid-micr5>3.0.co;2-f.
Aortic allotransplantation is a reliable procedure to study the evolvement of chronic rejection in mice. The progressive nature of this process in mice is characterized by diffuse and concentric myointimal proliferation which is inevitably associated with variable degrees of luminal constriction. These vascular changes are comparable to those that are witnessed in organ allografts undergoing chronic rejection in humans, underscoring its utility as a model of choice for the study of the development of this lesion. Whilst improved surgical technique has resulted in markedly enhanced graft survival, the results are far from being acceptable. Realizing this limitation, we embarked on developing a modified technique for aortic transplantation which would allow for improved graft survival in mice. A bypass conduit was created by end-to-side anastomosis of a segment of the donor's thoracic aorta into the infrarenal portion of the recipient's abdominal aorta. Using this technique, the graft survival was >98% with evidence in allotransplanted aorta of morphological changes pathognomonic of chronic rejection. On the contrary, no histopathological anomalies were discerned in aortic grafts transplanted across syngeneic animals. This modified surgical approach ameliorates the unacceptably high graft loss associated with earlier techniques, further extending the utility of this model as a tool to study the molecular and cellular mechanisms rudiment to the evolvement of chronic rejection.
主动脉同种异体移植是研究小鼠慢性排斥反应演变的可靠方法。该过程在小鼠中的进展性表现为弥漫性和同心性肌内膜增生,这不可避免地伴有不同程度的管腔狭窄。这些血管变化与人类同种异体器官慢性排斥反应中观察到的变化相似,突显了其作为研究该病变发展的首选模型的实用性。虽然改进的手术技术显著提高了移植物存活率,但结果仍远不能令人满意。意识到这一局限性后,我们着手开发一种改良的主动脉移植技术,以提高小鼠移植物的存活率。通过将供体胸主动脉的一段与受体腹主动脉肾下段进行端侧吻合来创建一个旁路管道。使用该技术,移植物存活率>98%,在同种异体移植的主动脉中出现了慢性排斥反应的特征性形态学变化。相反,在同基因动物间移植的主动脉移植物中未发现组织病理学异常。这种改良的手术方法改善了与早期技术相关的不可接受的高移植物丢失率,进一步扩展了该模型作为研究慢性排斥反应演变的分子和细胞机制工具的实用性。