聚—消旋乳酸—乙醇酸涂层支架置入小型猪冠状动脉后损伤处愈合过程的观察

Healing Process After Implantation of Poly-D,L-Lactide/GlycolicAcid Coated Stent Into Porcine Coronary

目的 :了解聚—消旋乳酸—乙醇酸 (PLGA)涂层支架置入冠状动脉后损伤处的愈合过程。方法 :用摩尔比 60∶40的消旋乳酸与乙醇酸共混聚合浸涂Dragon支架制成PLGA涂层支架作为涂层组 ,Dragon支架作为对照组 ,支架置入小型猪冠状动脉 ,7日期与 1个月期各 8只猪 ,每只置入两枚支架。支架置入前、后、终点时行冠状动脉造影 ,处死动物后分离取出支架置入段冠状动脉 ,固定并制备标本行扫描电子显微镜 (SEM )观察与组织学检查。结果 :7日期 1只于支架置入右冠状动脉后 3h、左冠状动脉前降支后 1 5h时死亡 ,组织学示损伤后 1 5h已经有血细胞附着 ,3h见到纤维素附着。所有支架置入成功。SEM示 7日期两组均完全内皮化 ,制备标本时撕裂处见内皮下为纤维素。组织学示 7日期对照组 2支、涂层组 1支支架血管段形成血栓 ;7日期内膜组织成份主要为附着的纤维素 ,偶见到平滑肌细胞、纤维母细胞 ,表面为一层内皮细胞 ,两组间无差异 ;1个月期内膜组分主要为纤维素样肌性组织及细胞外基质 ,内膜增生的程度两组间无差异。各组 1个月期内膜均较 7日期的明显增厚。结论 :冠状动脉损伤 +支架置入后的愈合过程为 ,血小板附着于损伤处→纤维素附着→内皮细胞与中层平滑肌细胞移行、增生 ,内膜增生。纤维素附着可能是内皮化的基础。

Objective:To give an insight into the healing process of the site where poly D,L lactide/glycolic acid (PLGA) coated stent was implanted.Methods:Dragon stents coated with PLGA(DL LA:GA for 60∶40 in mole) and Dragon stents(control group)were implanted into the coronary arteries of pigs for 7 days ( n =8) and 30 days ( n =8) Coronary angiography was performed before and after implantation and just before sacrofice Stented coronaries were harvested from the killed animals and prepared for scanning electron microscopy and histopathologic examination Results: One pig died of ventricular fibrillation 3 hours after implantation Histologically, blood cell attachment was found 1 5 hours and fibrin attachment was seen 3 hours after damaged Each stent was implanted into porcine coronary successfully All stented coronaries were reendothelialized completely at 7 days.When specimens were prep ared,subendothelial fibrin was seen in lacerated intima. At 7 days, thrombosis was found in 2 in control group and 1 in PLGA group The components of the intima consisted mainly of attached fibrin, some smooth muscle cells and fibroblast cells which were covered with a layer of endothelial cells At 30 days, the components of the intima consisted mainly of fibroid muscular tissue and extracellular matrix No significant difference was found in response to arterial injury between control group and PLGA group within one month, but neointima became greater at 30 days than at 7 days for both groups Conclusions:The healing process of the damaged coronary arteries and stent implantation may be as follows: platelet attachment to the wounded site→fibrin adhesion→migration and proliferation of the endothelial cells and vascular smooth muscle cells, and neointima development Fibrin adhesion to the wounded sites or stents may be the basis of reendothelialization Response to implantation of PLGA coated Dragon stents and Dragon stents into coronary arteries in porcine model revealed no difference within one month Complete reendothelialization of the wounded coronary arteries can not prevent intima from proliferating