雷帕霉素联合CD133抗体支架预防血管再狭窄的有效性和安全性

Effectiveness and safety of rapamycin combined with CD133 antibody stent in preventing vascular restenosis

背景:药物洗脱支架和单纯内皮修复型支架在治疗血管狭窄疾病时可见内皮化延迟以及植入后再狭窄的问题。作者既往的体外研究显示雷帕霉素联合CD133抗体支架可协同抵消抗增殖药物的内皮化延迟和内膜的过度增生。目的:在小型猪冠状动脉损伤模型中,分析雷帕霉素联合CD133抗体复合支架预防血管再狭窄的效果。方法:将冠状动脉损伤小型猪模型随机分为雷帕霉素组、CD133抗体组以及雷帕霉素/CD133抗体组,分别在损伤冠状动脉置入雷帕霉素支架、CD133抗体支架和雷帕霉素联合CD133抗体支架。动物实验于2019-03-15经沈阳医学院附属中心医院实验动物伦理委员会审批,审批号20190017。结果与结论:(1)3组支架植入后14 d和1个月时,内皮化程度存在差异,其中雷帕霉素组支架内皮覆盖程度低于CD133抗体组及雷帕霉素/CD133抗体组。(2)置入后3和6个月,雷帕霉素组和雷帕霉素联合CD133抗体组管腔狭窄率较低,但雷帕霉素支架周围组织存在明显的炎症反应,且CD133抗体支架可引起明显内膜增生及管腔狭窄。(3)提示雷帕霉素联合CD133抗体支架可在体内实现早期内皮化,促进内皮细胞修复,并在置入后降低周围组织炎症反应,且其6个月内抗增殖效果与雷帕霉素支架接近。

BACKGROUND: Drug eluting stents and endothelium stents for clinical treatment of vascular stenosis can lead to delayed endothelialization and restenosis. The authors’ previous in vitro studies have shown a rapamycin eluting stent combined with CD133 antibody can play a synergistic role to offset delayed endothelialization and intimal hyperplasia due to antiproliferative drugs.OBJECTIVE: To observe the efficacy of anti-CD133 antibody applied on a rapamycin eluting stent in the minipig coronary artery injury model.METHODS: Rapamycin-eluting stents, anti-CD133 antibody stents, and anti-CD133 antibody applied on rapamycin-eluting stents were implanted in minipig coronary arteries in the rapamycin group, CD133 antibody group, and rapamycin/CD133 antibody group, respectively. Animal experiments were approved by the Laboratory Animal Ethics Committee of Central Hospital Affiliated to Shenyang Medical College(approval No. 20190017) on March 15, 2019. RESULTS AND CONCLUSION:(1) There were differences in the endothelialization extent in the three groups at 14 days and 1 month after implantation. The stent endothelial coverage of the rapamycin group was lower than that of the CD133 antibody group and the rapamycin/CD133 antibody group.(2) At 3 and 6 months after implantation, the luminal stenosis rate of the rapamycin group and the rapamycin/CD133 antibody group was lower, but there was obvious inflammation in the surrounding tissues of the rapamycin stent, and the CD133 antibody stent could cause obvious intimal hyperplasia and lumen stenosis.(3) It is suggested that rapamycin combined with CD133 antibody stent can achieve early endothelialization in vivo, promote endothelial cell repair, and reduce the inflammation of surrounding tissues after implantation, and its anti-proliferative effect is similar to that of rapamycin stent within 6 months.