Hadoke P, Wainwright C L, Wadsworth R M, Butler K, Giddings M J
Department of Physiology & Pharmacology, University of Strathclyde, Glasgow, Scotland.
Coron Artery Dis. 1995 May;6(5):403-15. doi: 10.1097/00019501-199505000-00008.
A number of experimental models for the study of the pathogenesis of the restenotic process have been developed, although many fail to correlate the time courses of both functional and morphological alterations following balloon injury. Our aim was to develop a rabbit model of balloon injury, which studied both of these alterations in detail.
Male New Zealand White rabbits (12 weeks old) were fed a high-cholesterol diet for 4 weeks, after which they were subjected to balloon injury of the left subclavian artery. After surgery the animals were returned to a normal diet and sacrificed 2, 7, 15 or 30 days after angioplasty. Two further groups of animals were sacrificed either after 4 weeks of high-cholesterol feeding (no angioplasty) or 2 days after a sham angioplasty operation. Angioplasty-induced changes in vasoconstrictor [to 5-hydroxytryptamine (5-HT) and KCl] and endothelium-dependent (ACh and calcimycin) and endothelium-independent (sin-1) vasodilator responses were assessed in isolated vessel rings. Morphological analysis of the size and composition of neointima was also made at each timepoint.
Hypercholesterolaemia reduced the responsiveness of the subclavian arteries to the endothelium-dependent vasodilators carbachol and calcimycin; however, this responsiveness was restored after 7 days of a normal diet. The response to carbachol remained depressed in angioplastied arteries until 30 days after angioplasty, whereas recovery of relaxation to calcimycin was unaffected by angioplasty. Responses to 5-HT, KCl and sin-1 were unchanged by either hypercholesterolaemia or angioplasty. Morphological studies demonstrated the development of neointima in all rabbits after 7 days, reaching a maximum size after 15 days. All neointima stained for a smooth muscle actin. Accumulation of macrophages appeared in the media after 7 days and was present in the neointima after 15 days, and subsequently declined. Proliferating smooth-muscle cells were evident in the media 2 days after angioplasty, and in the neointima fro 7 days onwards.
In the rabbit subclavian artery, we have developed a model that describes fully the temporal development and characteristics of an intimal cellular response and functional changes following balloon injury.
尽管许多研究未能将球囊损伤后功能和形态学改变的时间进程联系起来，但已经建立了多种用于研究再狭窄过程发病机制的实验模型。我们的目的是建立一种兔球囊损伤模型，对这两种改变进行详细研究。
雄性新西兰白兔（12周龄）喂食高胆固醇饮食4周，之后对其左锁骨下动脉进行球囊损伤。手术后，动物恢复正常饮食，并在血管成形术后2、7、15或30天处死。另外两组动物在高胆固醇喂养4周后（未进行血管成形术）或假血管成形术操作2天后处死。在分离的血管环中评估血管成形术诱导的血管收缩反应[对5-羟色胺（5-HT）和氯化钾（KCl）]以及内皮依赖性（乙酰胆碱和钙霉素）和非内皮依赖性（sin-1）血管舒张反应。在每个时间点还对新生内膜的大小和组成进行形态学分析。
高胆固醇血症降低了锁骨下动脉对内皮依赖性血管舒张剂卡巴胆碱和钙霉素的反应性；然而，正常饮食7天后这种反应性得以恢复。在血管成形术后的动脉中，对卡巴胆碱的反应在血管成形术后30天一直受到抑制，而对钙霉素的舒张反应恢复不受血管成形术影响。高胆固醇血症或血管成形术对5-HT、KCl和sin-1的反应均无影响。形态学研究表明，所有兔子在7天后均出现新生内膜，15天后达到最大尺寸。所有新生内膜平滑肌肌动蛋白染色阳性。巨噬细胞在7天后出现在中膜，并在15天后出现在新生内膜中，随后减少。血管成形术后2天，增殖的平滑肌细胞在中膜明显可见，7天后在新生内膜中可见。
在兔锁骨下动脉中，我们建立了一种模型，该模型全面描述了球囊损伤后内膜细胞反应和功能变化的时间发展及特征。
