Yankah A C, Wottge H U, Müller-Ruchholtz W
German Heart Institute, Berlin.
Ann Thorac Surg. 1995 Aug;60(2 Suppl):S146-50. doi: 10.1016/0003-4975(95)00290-2.
This study was designed to determine the effect of short-course cyclosporin A therapy (10 mg/kg daily for 14 days) on allograft valve survival across the histocompatibility barriers in the following rat models; (1) syngeneic Lewis to Lewis (herein referred to as autografts), (2) weakly allogeneic AS to Lewis (RT1 compatible, non-RT1-incompatible), and (3) strongly allogeneic CAP to Lewis (RT1 and non-RT1-incompatible). Cyclosporin A-treated and untreated recipient animals (Lewis) received allovital and antibiotic-treated viable allografts implanted into the infrarenal aorta. Second-set skin grafting was performed 3 weeks after heterotopic valve implantation to test for immunogenicity and presensitization. The animals (Lewis) were sacrificed serially on days 20, 50, 100, and 150 for immunofluorescence study using mouse monoclonal antibodies (OX6) directed at class II endothelial surface antigens. The allografts in weakly allogenic strains showed no humoral response under a short course of cyclosporin A. The cyclosporin A-untreated allovital grafts and the viable (antibiotic-treated) valves demonstrated fibrocalcification on the 100th and 150th postoperative days, respectively. In conclusion, it seems that a short course of nontoxic immunosuppression could arrest allograft rejection and thus prevent early degeneration of allografts. Furthermore, antibiotic-treated viable allografts seemed to be more durable than allovital grafts.
本研究旨在确定短疗程环孢素A疗法(每日10mg/kg,共14天)对以下大鼠模型中跨越组织相容性屏障的同种异体移植瓣膜存活的影响:(1)同基因Lewis大鼠之间的移植(以下简称自体移植),(2)弱异体AS大鼠到Lewis大鼠的移植(RT1相容,非RT1不相容),以及(3)强异体CAP大鼠到Lewis大鼠的移植(RT1和非RT1不相容)。接受环孢素A治疗和未治疗的受体动物(Lewis大鼠)接受植入肾下腹主动脉的异体活性和经抗生素处理的活性同种异体移植物。在异位瓣膜植入3周后进行二次皮肤移植,以测试免疫原性和预致敏情况。在第20、50、100和150天连续处死动物(Lewis大鼠),使用针对II类内皮表面抗原的小鼠单克隆抗体(OX6)进行免疫荧光研究。在短疗程环孢素A治疗下,弱异体菌株中的同种异体移植物未显示体液反应。未用环孢素A处理的异体活性移植物和活性(经抗生素处理)瓣膜分别在术后第100天和150天出现纤维钙化。总之,似乎短疗程的无毒免疫抑制可以阻止同种异体移植排斥反应,从而防止同种异体移植物的早期退化。此外,经抗生素处理的活性同种异体移植物似乎比异体活性移植物更耐用。