抗CD34抗体优化雷帕霉素洗脱支架疗效的实验研究

目的 评价抗CD34抗体对雷帕霉素洗脱支架早期再内皮化以及远期抗再狭窄的影响.方法 将裸金属支架(BMS)、雷帕霉素洗脱支架(SES)和抗CD34抗体与雷帕霉素洗脱联合支架(ASES)随机置入到22头中华小型猪的冠状动脉内(共置入15枚BMS、17枚SES和16枚ASES).10头中华小型猪在置入支架(共置入6枚BMS、7枚SES和7枚ASES)后2周,另外12头中华小型猪在置入支架(共置入9枚BMS、10枚SES和9枚ASES)后3个月,进行冠状动脉造影及冠状动脉内光学相干断层成像( OCT)检查,并在处死动物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)支架术后2周,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均未发现支架内血栓及小的附壁血栓.对OCT图像的分析显示,ASES新生内膜覆盖率显著高于SES (55.56±35.27)％比(41.82±23.28)％,P＜0.05];ASES平均内膜覆盖厚度不但显著高于SES(89.0±5.0)μm比(32.0±4.9) μm,P＜0.01],而且显著高于BMS( 89.0±5.0) μ,m比(44.0±7.2)μm,P＜0.01].病理组织学观察及扫描电镜观察显示,ASES和BMS新生内膜覆盖水平及质量均优于SES.(2)支架术后3个月,定量冠状动脉造影显示ASES晚期支架内管腔丢失显著低于BMS (0.18±0.06)mm比(0.35±0.06)mm,P＜0.05];对OCT图像的分析显示,ASES和SES新生内膜增生百分比均显著低于BMS (34.75±2.64)％和(35.63±2.07)％比(48.28±3.25)％,均P＜0.01];组织病理学分析显示,ASES和SES面积再狭窄百分比均显著低于BMS组(28.65±5.64)％和(29.33±6.07)％比(46.18±8.25)％,均P＜0.05].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2周对再内皮化的抑制作用,同时没有削弱雷帕霉素洗脱支架术后3个月的抗再狭窄效能.

Stents coated with sirolimous and anti-CD34 antibody can optimize the performance of sirolimous-eluting stents

Objective To investigate the impact of the stents coated with sirolimous and anti-CD34 antibody on the short-term re-endothelialization and the long-term restenosis in Chinese Minipigs.Methods Three different types of stents bare-metal stent ( BMS ),sirolimous-eluting stent ( SES ) and anti-CD34 antibody and sirolimous-coated stent (ASES) ] were randomly implanted in the coronary arteries of 22Chinese Minipigs.At two weeks after stenting,coronary angiography and optical coherence tomography (OCT) were performed in 10 experimental animals.At three months after stenting,coronary angiography and OCT were performed in the remaining 12 experimental animals.Histopathologic examination was 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 at two weeks post stenting.OCT analysis showed that 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 ＜ 0.05 ].The mean thickness of neointima in ASES group was significantly higher than in SES group (89.0+5.0)1.μn vs.(32.0 +4.9) μm,P＜O.O1] and BMS group (89.0 +5.0) μm vs.(44.0 ± 7.2) μm,P ＜ 0.01].Histopathologic and scanning electron microscopy examinations demonstrated that the covering level and quality of stent struts by neointima in BMS and ASES group were both better than in SES group.(2) At three months follow-up,quantitative coronary angiography analysis found that late instent lumen loss in ASES group was significantly lower than in BMS group (0.18 ±0.06)mm vs.(0.35 ±0.06)mm,P ＜ 0.05].OCT analysis showed that the percent neointimal hyperplasia in ASES and SES group was significantly lower than in BMS group ( 34.75 + 2.64) ％ and ( 35.63 + 2.07 ) ％ vs.(48.28 ±3.25) ％,both P ＜ 0.01 ].Histopathologic analysis demonstrated that the percent areal restenosis of ASES and SES group were both significantly lower than that of BMS group (28.65 + 5.64)％ and (29.33 ±6.07)％ vs.(46.18 +8.25)％,both P ＜0.05].Conclusion The stents coated with anti-CD34 antibody and sirolimous can attenuate the inhibitory effect of sirolimous on the re-endothelialization at two weeks after stenting and the anti-hyperplasia effect of sirolimous at three months after stenting.