Bellón J M, Buján J, Jurado F, Hernando A, Honduvilla N G, Dominguez B
Department of Morphological Sciences and Surgery, University of Alcalá de Henares, Madrid, Spain.
Eur Surg Res. 1996;28(1):39-48. doi: 10.1159/000129438.
A study was made of the effect of cyclosporin A on intimal hyperplasia 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 implanted in right common iliac artery. Two groups were established: group I (control), consisting of 25 animals subjected only to arterial autograft, and group II (preoperative cyclosporin A), also consisting of 25 animals, which received a daily subcutaneous dose of 5 mg/kg cyclosporin A (Sandimmun, Sandoz) for 4 days before the surgical procedure. The animals were sacrificed on postoperative days 7, 14, 21, 30 or 50. Specimens were studied by optical microscopy, transmission and scanning electron microscopy, autoradiography, and morphometry. Endothelialization of the graft zone was slow in the cyclosporin-treated group. Hyperplasia was delayed notably, but at 30 days the hyperplastic process had improved and at 50 days it was similar to that of the control group. In the cyclosporin-treated group, thymidine was not taken up by the medial layer; the absence of medial thymidine uptake correlated with ultrastructural evidence of medial degeneration with lipid vacuolization of the smooth muscle cells and the presence of macrophages. These results suggest that cyclosporin A does not inhibit intimal hyperplasia but instead delays its occurrence, probably because of the drug's toxicity for smooth muscle cells.
在动脉自体移植实验模型中，对环孢素A对内膜增生的影响进行了一项研究。选用了50只体重250 - 300克的雌性斯普拉格 - 道利大鼠。采用显微外科技术，将一段长度约为5毫米的动脉自体移植物植入右髂总动脉。设立了两组：第一组（对照组），由仅接受动脉自体移植的25只动物组成；第二组（术前环孢素A组），也由25只动物组成，在手术前4天每天皮下注射5毫克/千克环孢素A（山地明，山德士公司）。在术后第7、14、21、30或50天处死动物。通过光学显微镜、透射和扫描电子显微镜、放射自显影及形态计量学对标本进行研究。在环孢素治疗组中，移植区的内皮化缓慢。增生明显延迟，但在30天时增生过程有所改善，在50天时与对照组相似。在环孢素治疗组中，中层未摄取胸苷；中层胸苷摄取的缺乏与中层变性的超微结构证据相关，中层变性表现为平滑肌细胞的脂质空泡化和巨噬细胞的存在。这些结果表明，环孢素A并不抑制内膜增生，而是延迟其发生，这可能是由于该药物对平滑肌细胞的毒性作用。
