三氧化二砷洗脱支架诱导猪损伤冠脉平滑肌细胞凋亡

目的观察三氧化二砷（As2O3）多聚左旋乳糖酸（PLLA）涂层支架对猪损伤冠脉平滑肌细胞的凋亡诱导作用及机制。方法在6头小型家猪的冠脉内随机植入裸金属支架、PLLA涂层支架、雷帕霉素洗脱支架和As2O3洗脱支架，7天后处死，TUNEL法检测支架段血管平滑肌细胞凋亡率、免疫组化和Western blot法检测凋亡蛋白p53和增殖细胞核抗原（PCNA）蛋白表达，体外观察As2O3对大鼠血管平滑肌细胞的凋亡诱导作用和p53表达。结果与裸支架和PLLA涂层支架相比，雷帕霉素洗脱支架和As2O3洗脱支架植入局部平滑肌细胞凋亡率以及p53表达明显增多，尤其以As2O3洗脱支架最为明显（P〈0．01），雷帕霉素洗脱支架和As2O3洗脱支架植入局部PCNA表达较裸支架和PLLA涂层支架明显减少（P〈0．01），但二者间无显著性差异（P〉0．05）。体外细胞培养显示As2O3呈剂量依赖性的诱导大鼠血管平滑肌细胞凋亡和p53蛋白的表达。结论As2O3洗脱支架具有诱导猪损伤冠脉平滑肌细胞凋亡的作用，且较雷帕霉素洗脱支架更明显，其凋亡诱导作用和增加局部细胞p53表达有关。

Arsenic trioxide-eluting stents induce apoptosis of vascular smooth muscle cells in injured coronary arteries in pigs

Objective To observe the apoptosis inducing effect of eluting stents coated with arsenic trioxide （As2O3 ） suspended in poly-L-lactic acid （PLLA） on vascular smooth muscle cells（VSMCs） of injured coronary arteries in pigs. Methods Bare metal stents, PLLA coating stents, rapamycin-eluting stents and As2O3-eluting stents were randomly implanted into coronary arteries in six pigs. Animals were euthanized and coronary arteries were isolated 7 days after stents implantation. The apoptotic cells were determined by TUNEL staining and the expression of p53 and PCNA were determined by Western blot analysis and immunohistochemistry. The apoptosis inducing effect of As2O3 on cultured rat VSMCs was determined by Annexin- V/PI staining. Results As compared to bare metal stents and PLLA coating stents, rapamycin-eluting stents and As2O3 eluting stents induced more TUNEL-positive and p53-positive VSMCs, and the positive VSMCs percentage in As2O3 eluting stents group was highest（ P 〈 0.01 ）. Rapamycin-eluting stents and As2O3 eluting stents identically and significantly reduced the PCNA expression （ P 〈 0.01 ）. Annexin-V/PI staining showed As2O3 dose-relatedly induced apoptosis of cultured rat VSMCs and increased the p53 expression. Conclusion As2O3 -eluting stents can induce apoptosis of VSMCs of injured coronary arteries in pigs, which is more significant than rapamycin-eluting stents and related to the increase of p53 expression.