三氧化二砷洗脱支架对犬冠状动脉支架术后内膜平滑肌细胞及Ⅲ型胶原的影响

Effects of Control-releasing Arsenic Trioxide-eluting Stent on Intimal Smooth Muscle Cells and Type Ⅲ Collagen in Canine Coronary Artery Post-stent Model

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中文关键词: 三氧化二砷支架平滑肌细胞 Ⅲ型胶原

英文关键词:arsenic trioxide stent smooth muscle cells type Ⅲ collagen

基金项目:

作者	单位
赵军礼	上海交通大学附属第一人民医院心内科上海市心脏急救中心
孙宝贵	上海交通大学附属第一人民医院心内科上海市心脏急救中心
温沁竹	上海交通大学附属第一人民医院心内科上海市心脏急救中心
张建军	上海交通大学附属第一人民医院心内科上海市心脏急救中心
金炜	上海交通大学附属第一人民医院心内科上海市心脏急救中心
薛吉祥	上海交通大学附属第一人民医院心内科上海市心脏急救中心
张彩凤	上海交通大学附属第一人民医院心内科上海市心脏急救中心
刘少稳	上海交通大学附属第一人民医院心内科上海市心脏急救中心

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中文摘要:

目的探讨不同剂量三氧化二砷(As2O3)控释洗脱支架对犬冠状动脉支架术后内膜平滑肌细胞(SMC)和Ⅲ型胶原的影响及安全性。方法制作聚甲基丙烯酸丁酯/纳米二氧化硅-聚乳酸/乙醇酸双涂层As2O3控释洗脱支架,As2O3剂量分别为0(对照组)、1.6μg/mm2(小剂量组)、2.4μg/mm2(中剂量组)和3.2μg/mm2(大剂量组)。支架、血管以1.3∶1比例随机置入24只犬冠状动脉回旋支或前降支,单纯涂层支架为对照组(各组6只)。术后4周处死,分析支架置入段血管组织形态学变化,免疫组化法检测SMC及Ⅲ型胶原的表达。结果各组光镜下未见内膜下出血及中膜、外膜坏死,无附壁血栓及炎性细胞浸润,药物组尤其是大剂量组SMC及Ⅲ型胶原免疫组化阳性表达明显弱于对照组;扫描电镜显示各组内皮完整。组织形态学分析结果显示:大、中、小剂量组新生内膜面积、管腔面积狭窄率均明显小于对照组(P<0.01),平均管腔直径显著大于对照组(P<0.01);小剂量组与大、中剂量组各指标比较差异有统计学意义(P<0.01);大、中剂量组各指标比较,差异无统计学意义(P>0.05)。结论 As2O3控释洗脱支架安全可行,通过减少SMC和Ⅲ型胶原表达呈剂量依赖性抑制犬冠状动脉支架置入后内膜增生,具有显著的防治再狭窄作用。

英文摘要:

Objective To study the safety and efficacy of control-releasing arsenic trioxide(As2O3)-eluting stent on intimal smooth muscle cells (SMC) and type Ⅲ collagen (CⅢ) in canine coronary artery post-stent model. Methods Twenty-four experimental canines were equally divided into 4 groups,the three tested groups were deployed by stents with different dosage of As2O3 (1.6 μg/mm2,2.4 μg/mm2 and 3.2 μg/mm2 in low,median and high dose groups,respectively) and coated with polybutyl methacrylate/nano silica and poly-lactide-co-glycolide in mild oversizing (stent/vessel ratio of 1.3:1) in left anterior descending (LAD) or circumflex coronary arteries (LCX),while the control group only by simple coated stent without As2O3. The effect was assessed 4 weeks after stent implantation in terms of vascular histomorphology,and changes of SMC and CⅢ expressions were detected using immunohistochemical analysis. Results Subintimal hemorrhage,medial/adventitial necrosis,thrombosis and inflammatory cell infiltration were not found and integral endothelium could be seen under screening electron microscopy in all groups.Positive expression of SMC and CⅢ in the tested groups,especial in the high dose As2O3 group,was more weaker than that in control group. Histo-morphological analysis showed that the neo-genetic intimal area and vascular stenosis were lower,but the mean luminal diameter was larger in the three tested groups than that in the control group (P<0.01). Comparisons of various indices between tested groups treated by different doses of As2O3 showed that the difference between high/median dose vs. low dose was significant (P<0.01),but that between high dose vs. median dose was insignificant (P>0.05).Conclusion Control-releasing As2O3-eluting stent shows a reliable and safe effect in preventing and treating post-stent restenosis by its dose-dependent inhibition on expressions of SMC and CⅢ to suppress the neo-genesis of intimal hyperplasia.

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