雷帕霉素支架联合X线外照射预防支架置入后血管再狭窄的实验研究

摘要

目的:观察雷帕霉素支架、X射线照射及两者联合对支架置入术后血管内膜增生的影响,找出抑制内膜增生的理想方法及评价其安全性.方法:建立比格犬动脉粥样硬化血管支架置入的动物模型,随机分为对照组(仅行常规支架置入)、药物支架组、放射组及联合组,取实验动物的离体血管及空腹静脉血,分别检测其平均管腔面积、血管新生内膜平均增生面积、平滑肌细胞凋亡率及放疗前后静脉血常规.结果:血管平均厚度及血管新生内膜平均增生面积对照组最厚,联合组最低,放射组和药物支架组差异无统计学意义(P＞0.05).对照组凋亡相关蛋白Survivin和Bcl-2表达最高,Caspase-9表达最低；联合组凋亡相关蛋白Survivin和Bcl-2表达最低,Caspase-9表达最高；放射组和药物支架组凋亡相关蛋白表达差异无统计学意义(P＞0.05).放疗后第8天,放疗组与联合组的白细较前降低,但两者之间差异无统计学意义(P＞0.05),余各项指标放疗前后无明显变化.结论:与雷帕霉素支架和X线照射相比较,两者联合应用更能促进血管内皮细胞的凋亡,从而更好地抑制血管内膜的增生,且未显示有更多的副作用及并发症.%Objective:To find a way of inhibitting intimal hyperplasia and evaluation its security,the study investigates the effect on intimal hyprplasia after stent implantation with rapamycin,X ray irradiation and their combined.Methods:Establishing Beagle canine model of atherosclerosis vascular with stent implantation,the Beagle canines were randomly divided into control group,drug-coated stent group,radiation group and mixed group.To detecte the average area of lumen,the average neo-hyperplasia vascular endothelium,the apoptosis rate of vascular smooth muscle cells of the vascular of experimental animal.To detecte the routine of limosis vein blood before and after radiotherapy.Results:The average thickness of lumen and the average neo-hyperplasia vascular endothelium of control group were thickest,which of mixed group were thinnest,and which were no significant difference between drug-coated stent group and radiation group (P＞ 0.05).The expression of apoptosis-related proteins Survivin and Bcl-2 was the highest and caspase-9 was the lowest of control group,the expression of apoptosis-related proteins Survivin and Bcl-2 was the lowest and caspase-9 was the highest of mixed group,and the expression of apoptosis-related proteins were no significant difference between drug-coated stent group and radiation group (P＞ 0.05).The WBC was decreased of radiation group and mixed group at eighth days after radiotherapy,but which were no significant difference between radiation group and mixed group,and the other index of blood had no obvious change before and after radiotherapy.Conclusion:The mixed group can promote the apoptosis of vascular endothelial cells and inhibit intimal hyperplasia better than the rapamycin stent group and X-ray radiation group,and there was no more side effects and complications.