Hanke H, Haase K K, Hanke S, Oberhoff M, Hassenstein S, Betz E, Karsch K R
Department of Medicine, University of Tübingen, FRG.
Circulation. 1991 Apr;83(4):1380-9. doi: 10.1161/01.cir.83.4.1380.
Little is known about the mechanism(s) in the development of restenosis after excimer laser angioplasty. Thus, the rationale of this study was to determine the time course of intimal and medial smooth muscle cell (SMC) proliferation and histomorphological changes after experimental excimer laser treatment.
Laser ablation was performed in the right carotid artery of 34 New Zealand White rabbits after development of a fibromuscular plaque by repeated weak electrical stimulations. The vessels were excised 3, 7, 14, 21, 28, and 42 days after excimer laser treatment. Staining of alpha-actin was used to identify SMCs. In five rabbits (15%), a stenosis of more than 50% of luminal area was due to intimal proliferation of SMCs, and in four other rabbits, a total occlusion was due to organized thrombi. After the initial ablation of the performed plaque (13 +/- 6 intimal SMC layers) a continuous increase of intimal wall thickness was found from 7 +/- 6 SMC layers at 7 days to 28 +/- 5 intimal SMC layers at 28 days after excimer laser ablation (p less than 0.01). After 42 days, no additional increase of intimal thickening occurred. After bromodeoxyuridine labeling, the extent of cell proliferation (percent of cells undergoing DNA synthesis) in the intima and media was determined using a monoclonal antibody against bromodeoxyuridine. Immunohistological quantification of SMC proliferation in the intima revealed a significant increase of cells undergoing DNA synthesis at 3 (p less than 0.05) and 14 (p less than 0.01) days after laser treatment. Medial proliferation of SMCs was delayed and had a significant increase 7 days (p less than 0.05) after intervention. Twenty-one days after laser treatment, SMC proliferation in the intima as well as in the media was normalized.
The proliferative response of SMCs after experimental excimer laser treatment will occur as a dynamic process with a maximum of SMCs undergoing DNA synthesis during 14 days after laser ablation, resulting in an increase of intimal thickening within 4 weeks after laser treatment. The extent of intimal hyperplasia due to SMC proliferation after excimer laser treatment is comparable with the effect of transluminal balloon angioplasty in this experimental model.
关于准分子激光血管成形术后再狭窄发生的机制了解甚少。因此，本研究的目的是确定实验性准分子激光治疗后内膜和中膜平滑肌细胞（SMC）增殖的时间进程以及组织形态学变化。
通过反复弱电刺激在34只新西兰白兔的右颈动脉形成纤维肌性斑块后进行激光消融。在准分子激光治疗后3、7、14、21、28和42天切除血管。使用α-肌动蛋白染色来识别SMC。在5只兔子（15%）中，管腔面积狭窄超过50%是由于SMC的内膜增殖，在另外4只兔子中，完全闭塞是由于机化血栓。在对形成的斑块进行初始消融后（内膜SMC层为13±6层），发现内膜壁厚度持续增加，从准分子激光消融后7天的7±6层SMC增加到28天的28±5层内膜SMC（p<0.01）。42天后，内膜增厚没有进一步增加。在溴脱氧尿苷标记后，使用抗溴脱氧尿苷单克隆抗体确定内膜和中膜中细胞增殖的程度（进行DNA合成的细胞百分比）。内膜中SMC增殖的免疫组织学定量显示，激光治疗后3天（p<0.05）和14天（p<0.01）进行DNA合成的细胞显著增加。SMC的中膜增殖延迟，干预后7天显著增加（p<0.05）。激光治疗21天后，内膜和中膜中的SMC增殖恢复正常。
实验性准分子激光治疗后SMC的增殖反应是一个动态过程，在激光消融后14天内进行DNA合成的SMC数量最多，导致激光治疗后4周内内膜增厚增加。在该实验模型中，准分子激光治疗后由于SMC增殖导致的内膜增生程度与腔内球囊血管成形术的效果相当。
