抗CD34抗体抵消雷帕霉素洗脱支架内皮延迟修复研究

The union of anti-CD34 antibody can offset the inhibitory effect of sirolimous-eluting stents on the re-endothelialization

目的:雷帕霉素洗脱支架在降低再狭窄风险的同时,通过抑制血管再内皮化,可能增加支架内血栓发生风险,抗CD34抗体通过特异捕获血液中内皮祖细胞,加速支架术后血管再内皮化。本研究目的是将抗CD34抗体涂敷到雷帕霉素洗脱支架上,通过实验小猪支架术后不同时间造影,随访评价抗CD34抗体对雷帕霉素洗脱支架早期再内皮化的影响。方法:将3种不同类型的支架包括金属裸支架(bare-metal stents,BMS)、雷帕霉素洗脱支架(sirolimous-eluting stents,SES)和抗CD34抗体与雷帕霉素洗脱联合支架(anti-CD34 antibody and sirolimous-eluting combined stents,ASES)随机植入到符合条件的10头中华小型猪冠状动脉内(共植入了6个BMS、7个支架和7个ASES),支架植入术后2 w,进行冠状动脉造影及冠状动脉内光学相干断层成像(optical coherence tomography,OCT)检查;动物处死后,对支架段冠状动脉进行病理组织学检查及扫描电镜观察。结果:1.通过对冠状动脉造影、OCT图像及支架段冠状动脉的病理组织学的观察分析,均未发现支架内血栓及小的附壁血栓。2.在2 w OCT检查图像上,ASES新生内膜覆盖率显著高于SES[(55.56±35.27)%vs.(41.82±23.28)%,P=0.047],ASES平均内膜覆盖厚度不但显著高于SES[(89±5.0)μm vs.(32±4.9)μm,P<0.001]、还高于BMS[(89±5.0)μm vs.(44±7.2)μm,P=0.001]。病理组织学观察及扫描电镜观察也显示,ASES和BMS新生内膜覆盖水平及质量均优于SES。结论:将抗CD34抗体联合应用到雷帕霉素洗脱支架上,能够显著抵消后者在支架术后早期对再内皮化的抑制作用。

Objective：Though sirolimous-eluting stents can reduce the risk of restenosis,it may increase the risk of in-stent thrombosis by delaying the re-endothelialization after stenting.Anti-CD34 antibody may improve the re-endothelialization after stenting by specifically capturing the endothelial progenitor cells in blood.The aim of this study is to investigate the effects of the union of anti-CD34 antibody to sirolimous-eluting stents on the short-term re-endothelialization.Methods：Three different types of stents were randomly implanted in the coronary arteries of ten Chinese minipigs,including bare-metal stent（BMS）,sirolimous-eluting stent（SES） and anti-CD34 antibody and sirolimous-eluting combined stent（ASES）.At two weeks after stenting,coronary angiography and optical coherence tomography（OCT） were performed in ten experimental animals.Histopathologic examination and scanning electron microscopy were performed on the coronary artery segments containing stent after the animals were executed.Results：1.No in-stent thrombosis and parietal thrombus were found by coronary angiography,OCT and histopathologic examination.2.At the two weeks follow-up,by OCT analysis,the covered ratio of stent struts by neointima in ASES group was higher than in SES group [（55.56±35.27）% vs.（41.82±23.28）%,P=0.047];the mean thickness of neointima in ASES group was significantly higher than in SES group [（89±5.0）μm vs.（32±4.9）μm,P0.001] and BMS group [（89±5.0）μm vs.（44±7.2）μm,P=0.001].Histopathologic examination and scanning electron microscopy both showed that the covering level and quality of stent struts by neointima in BMS and ASES group were both better than in SES group.Conclusion：The union of anti-CD34 antibody to sirolimous-eluting stents can offset the inhibitory effect of it on the re-endothelialization at short-term after stenting.