可控性生物吸收镍合金药物洗脱支架对支架内再狭窄的作用与安全性分析研究

Analysis of safety and efficacy of controllable bioabsorbable nickel alloy drug⁃eluting stents

目的观察可控性生物吸收镍合金药物洗脱支架置入兔腹主动脉的安全性及有效性。方法选取20只雄性新西兰大白兔,随机分到金属裸支架组(BMS组)和镀镍不锈钢支架组(Ni‐BMS组),每组10只,体重2.5~3.0 kg,4~6个月龄。兔子适应性喂养3 d,术前3 d开始喂服阿司匹林25 mg/d,硫酸氢氯吡格雷片20 mg/d,术前动物严格禁食12 h,准确测量体重。本研究以术后30 d为观察终点。检测血管的外弹力膜围绕面积、内弹力膜围绕面积、管腔面积,新生内膜面积为及面积狭窄百分比、增殖细胞阳性指数、凋亡细胞阳性指数及安全性。结果Ni‐BMS组管腔面积大于BMS组(P<0.05)。Ni‐BMS组及BMS组内弹力板面积和外弹力板面积差异无统计学意义(P>0.05)。Ni‐BMS组新生内膜面积小于BMS组(P<0.05),Ni‐BMS组面积狭窄百分比小于金属裸支架(P<0.05)。BMS组与Ni‐BMS组炎症积分、损伤积分和内皮化积分差异无统计学意义(P>0.05)。术后30 d,Ni‐BMS组细胞阳性指数低于BMS组(P<0.05),Ni‐BMS组凋亡细胞阳性指数高于BMS组(P<0.05)。实验兔子于术前、观察终点的血液指标2组间未见明显异常、重要脏器及病理未见明显改变。结论与金属裸支架相比可控性生物吸收镀镍支架在早期可以抑制支架内新生内膜形成,减少再狭窄的发生。可控性生物吸收镀镍支架通过抑制平滑肌细胞增殖、促进其凋亡来抑制内膜增生,可能有预防再狭窄的发生的作用。可控性生物吸收镀镍支架植入短期内全身系统安全性良好,具有较好的生物相容性。

Objective To observe the safety and efficacy of controllable bioabsorbable nickel alloy drug‐eluting stent implanted into the abdominal aorta of rabbits.Methods Twenty male New Zealand white rabbits with a weight of 2.5-3.0 kg and an age of 4‐6 months were selected and randomly assigned as the bare metal stent group(or the BMS group)and the nickel‐plated stainless steel stent group(or the Ni‐BMS group),each consisting of 10 animals.The rabbits were adaptively fed for 3 days,and then 3 days before surgery were fed with aspirin at doses of 25 mg/d and clopidogrel bisulfate tablets at doses of 20 mg/d.The animals were strictly fasted for 12 h before operation,and body weights were accurately measured.The end point of observation was 30 days after stent implantation.The stent was pre‐installed on the balloon,and all surgical instruments were sterilized for later use.Detections were made at the surrounding area of the outer elastic membrane,the surrounding area of the inner elastic membrane,the lumen area,the area of the neointima,the percentage of area stenosis.The positive index of proliferating cells,and the positive index of apoptotic cells,and the safety of animals were detected as well.Results The lumen area of the Ni‐BMS group was larger than that of the BMS group(P<0.05).There were no significant differences in the area of inner elastic plate and outer elastic plate,when comparisons were made between the 2 groups(P>0.05).The area of neointimal in the Ni‐BMS group was smaller than that in the BMS group(P<0.05),and the area stenosis percentage in the Ni‐BMS group was smaller than that in the bare metal stent group(P<0.05).There was no statistical significance in the scores of inflammation,injury and endothelialization,when comparisons were made between the 2 groups(P>0.05).28 days after operation,the positive index of the cells in the Ni‐BMS group was lower than that in the BMS group(P<0.05),while the positive index of apoptotic cells in the Ni‐BMS group was higher than that in the BMS group(P<0.05).Experimntal results indicated that there was no obvious abnormality in the blood indexes of the experimental rabbits,before operation and at the observation end point,and pathological changes and lesions of important organs could hardly be noticed.Conclusion Compared with bare metal stents,controllable bioabsorbable nickel‐plated stents could inhibit formation of neointimal in the stent in the early stage and reduce the occurrence of restenosis.Controllable bioabsorbable nickel‐plated stents could inhibit intimal hyperplasia by inhibiting the proliferation of smooth muscle cells and promoting apoptosis,which might have the effect of preventing the incidence of restenosis.Controllable bioabsorbable nickel‐plated stent implantation seemed to have good systemic safety and good biocompatibility in the short term.