CD105抗体支架内再狭窄及血栓形成的实验研究

Efficacy of stents coated with antibody against CD105 on preventing restenosis and thrombosis in minipigs

目的 探讨CD105抗体支架预防再狭窄及血栓形成的作用.方法 将CD105抗体支架（CD105支架组）、Cypher支架（Cypher支架组）及316L不锈钢金属裸支架（裸支架组）各30枚分别置入30只小型猪的冠状动脉内.术后7和14 d,通过冠状动脉造影对冠状动脉进行量化分析,以扫描电镜观察血管内皮的变化,并在光镜下观察血管形态学的改变.结果 术后7 d,CD105支架组、裸支架组支架内皮化积分均高于Cypher支架组（1.71 4±0.49、1.50 4±0.67比1.08±0.29,P均〈0.05）;CD105支架组[（23.8±3）%、（0.14±0.10）mm]、Cypher支架组[（21.7±2）%、（0.11±0.08）mm]管腔狭窄率和晚期管腔丢失与裸支架组[（24±3）%、（0.12±0.09）mm]差异无统计学意义.术后14 d,CD105支架组、Cypher支架组晚期管腔丢失小于裸支架组[（0.29±0.28）mm、（0.28±0.02）mln比（0.41±0.01）mm,P均〈0.05];支架内皮化积分CD105支架组、裸支架组均高于Cypher支架组（1.78±0.49、1.50±0.67比1.08±0.29,P均〈0.05）,CD105支架组高于裸支架组（P〈0.05）;CD105支架组、Cypher支架组管腔狭窄率均小于裸支架组[（23.8±4）%、（24.2±2）%比（38.0±3）%,P均〈0.05],CD105支架组与Cypher支架组差异无统计学意义.新生内膜面积CD105支架组、Cypher支架组小于裸支架组[（0.88±0.08）mm^2、（0.89±0.12）mm2比（1.00±0.14）mm^2,P均〈0.05],CD105支架组与Cypher支架组差异无统计学意义.术后7和14 d,各组间损伤积分及炎症积分差异无统计学意义,且均无支架内血栓形成.术后7和14 d,扫描电镜显示CD105支架组血管内皮覆盖程度均明显高于Cypher支架组和裸支架组.结论 CD105抗体支架能有效预防支架内再狭窄及血栓形成.

Objective Novel stents loaded with antibody against CD105 were analyzed for their potential to limit coronary neointima formation and to accelerate endothelialization by attracting activated endothelial cell. Methods Thirty Stents coated with antibody against CD105, thirty unloaded polymer, and thirty bare metal stents were deployed in 90 coronary arteries of 30 minipigs. Oral aspirin （300 mg before operation and 100 mg post operation） and clopidogrel （300 mg before operation and 75 mg post operation） were orally administrated. Coronary artery quantitative analysis was completed by coronary arteriography,the vascular endothelium changes were observed under scanning electron microscope and the vascular morphological changes were observed under light microscope 7 and 14 days after operation. Results Complete procedural and angiographic success was achieved in all 30 minipigs. There were no major adverse cardiac and cerebrovascular events. At 7 days, there was no difference for mean neointimal area and percent rea stenosis among various groups. At 14 days, endothelialization scores were significantly higher in the CD10S antibody-loaded stents and bare metal stents group than in sirolimus-eluting stents group （1.78 ± 0.49, 1. 50±0. 67 vs. 1. 08±0. 29, all P 〈 0. 05 ）, mean percent area stenosis in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [ （23. 8± 4） % , （24. 2±2）% vs. （38.0 ±3）% , all P 〈0.05] ,mean angiographic late luminal loss in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [ （0. 29±0. 28） mm, （0. 28±0. 02） mm vs. （0.41±0. 01） mm, all P 〈 0. 05 ]. There was no difference for mean percent area stenosis in the CD105 antibody-loaded stents and sirolimus-eluting stents group. The mean neointimal area in the CD105 antibody-loaded stents,and sirolimus-elutingstents group were less than that in bare metal stents group [（0.88±0.08） mm^2, （0. 89 ±0. 12mm）2 vs. （ 1. 00 ±0. 14） mm^2 , all P〈0.05] and there was no difference for the mean neointimal area in the CD105 antibody-loaded stents and sirolimus-eluting stents group. At 7 and 14 days, there was no difference for the injury score and the inflammation score among various groups, scanning electron microscopy evidenced enhanced endothelial coverage on CD105 antibody-loaded stents compared to sirolimus-eluting stents group. Conclusion Stent coated with antibody against CD105 could effectively reduce in-stent restenosis and accelerate endothelialization in th eminipigs.