Buján J, Bellón J M, Jurado F, Hernando A, Contreras L
Department of Morphological Sciences and Surgery, Faculty of Medicine, University of Alcalá de Henares, Madrid, Spain.
Histol Histopathol. 1995 Jul;10(3):567-76.
The objective of this ultrastructural study was to assess the effects of cyclosporine A (CsA) in an experimental model of arterial autograft. Fifty female Sprague-Dawley rats weighing 250-300 g were employed. Using a microsurgical technique, an arterial autograft measuring approximately 5 mm in length was placed in the right common iliac artery. Two groups were established: group I (control), consisting of 25 animals subjected only to arterial autograft; and group II (pre- and postoperative CsA), also consisting of 25 animals which received a daily subcutaneous dose of 5 mg/kg CsA (Sandimmun, Sandoz) on the four days preceding the surgery and thereafter, until sacrifice. The animals were sacrificed on postoperative day 7, 14, 21, 30 and 50. The specimens (autografts) obtained were studied under transmission and scanning electron microscopes. In the control group, the process of endothelialization of the graft was completed by day 14. In the CsA-treated group, restoration of the endothelium took 50 days. The development of intimal hyperplasia was delayed in the treated group. There were no morphological changes in its structure when compared to the control group. The tunica media had thinned in the treated grafts, with loss of smooth muscle cells, fragmentation and lysis of the elastic lamina, presence of lipid-filled macrophages, and muscle cells with cytoplasmic lipid vacuoles. In our opinion, these results suggest that the action of CsA mainly targets on the endothelium and smooth muscle cells, exerting a toxic effect in an in vivo arterial graft model.
本超微结构研究的目的是评估环孢素A（CsA）在动脉自体移植实验模型中的作用。选用50只体重250 - 300 g的雌性Sprague-Dawley大鼠。采用显微外科技术，将一段长度约5 mm的动脉自体移植物植入右侧髂总动脉。分为两组：I组（对照组），由25只仅接受动脉自体移植的动物组成；II组（术前及术后使用CsA组），同样由25只动物组成，这些动物在手术前4天及之后每天皮下注射5 mg/kg CsA（山地明，山德士公司），直至处死。在术后第7、14、21、30和50天处死动物。对获取的标本（自体移植物）进行透射电子显微镜和扫描电子显微镜观察。对照组中，移植物的内皮化过程在第14天完成。在CsA处理组中，内皮恢复需要50天。处理组内膜增生的发展延迟。与对照组相比，其结构无形态学变化。处理后的移植物中，中膜变薄，平滑肌细胞丢失，弹性膜断裂溶解，出现充满脂质的巨噬细胞以及含有细胞质脂质空泡的肌细胞。我们认为，这些结果表明CsA的作用主要靶向内皮细胞和平滑肌细胞，在体内动脉移植模型中发挥毒性作用。
