Buján J, Bellón J M, Jurado F, Dominguez B, Gimeno M J, García-Honduvilla N, Hernando A
Department of Morphological Sciences and Surgery (Surgical Research Laboratory), School of Medicine, University of Alcalá de Henares, Madrid, Spain.
J Cardiovasc Pharmacol. 1996 Aug;28(2):285-93. doi: 10.1097/00005344-199608000-00016.
Pharmacologic modulation by an inhibitor of angiotensin-converting enzyme (IACE: cilazapril) of vascular proliferative response to a full-thickness arterial injury (autograft) was studied in rats. An arterial autograft 5 mm long was made in the right common iliac artery of 50 female Sprague-Dawley rats (weight 250-300 g) by microsurgical techniques. The animals were divided into two study groups: group I (controls), 20 animals that underwent arterial autograft but received no other treatment; and group II (cilazapril-treated), 20 rats that underwent arterial autograft and received cilazapril (Roche), 10 mg/day orally (p.o.) in an excipient of 2% arabic gum, for 4 days before operation. Animals were killed on postoperative days 7, 14, 21, 30, and 50, and grafts were studied by light microscopy, scanning and transmission electron microscopy, and morphometry. In the control group, the hyperplasic response had begun by postoperative day 14 and was established by postoperative day 50. In the medial layer, the muscle cells changed in phenotype from contractile to secretory cells. The adventitia had a highly proliferative appearance. In the cilazapril-treated group, fibrin deposits and platelets formed a layer on the internal elastic lamina. This layer appeared to evolve toward an intimal hyperplasia that became quantifiable by postoperative day 21. The medial layer was clearly thinned and showed intense accumulation of lipid microvacuoles, elastic degeneration, and vacuolized cells. Our results suggest that the use of an inhibitor of ACE modified the origin of the intimal hyperplasia in the arterial autograft model. Enhancement of the thrombogenicity of the luminal surface favors myointimal development by thrombus reorganization.
在大鼠中研究了血管紧张素转换酶抑制剂（IACE：西拉普利）对全层动脉损伤（自体移植）后血管增殖反应的药理调节作用。采用显微外科技术在50只雌性Sprague-Dawley大鼠（体重250 - 300克）的右髂总动脉制作5毫米长的动脉自体移植。动物被分为两个研究组：第一组（对照组），20只接受动脉自体移植但未接受其他治疗的动物；第二组（西拉普利治疗组），20只接受动脉自体移植并在术前4天口服（p.o.）西拉普利（罗氏公司生产）10毫克/天，赋形剂为2%阿拉伯胶的大鼠。在术后第7、14、21、30和50天处死动物，通过光学显微镜、扫描和透射电子显微镜以及形态计量学研究移植物。在对照组中，增生反应在术后第14天开始，并在术后第50天确立。在内膜层，肌肉细胞表型从收缩细胞转变为分泌细胞。外膜有高度增殖的外观。在西拉普利治疗组中，纤维蛋白沉积物和血小板在内弹力膜上形成一层。这一层似乎发展为内膜增生，到术后第21天变得可量化。内膜层明显变薄，显示脂质微泡大量积聚、弹性变性和空泡化细胞。我们的结果表明，使用ACE抑制剂改变了动脉自体移植模型中内膜增生的起源。管腔表面血栓形成性的增强通过血栓重组促进肌内膜发育。
