Triptolide涂层支架对猪冠脉内膜增殖及血管内皮生长因子、细胞间黏附分子-1表达的影响

Effect of a triptolide-eluting stent on neointimal hyperplasia and the expression of VEGF and ICAM-1 in pigs

目的研究雷公藤内酯醇涂层支架（triptolide eluding stent，TES）置入猪冠状动脉后对血管内膜增生、炎性因子激活、血管损伤、术后再狭窄的影响及支架的安全性。方法12只健康小型猪随机分为3组，分别植入雷公藤内酯醇涂层支架（100μg）、雷帕霉素洗脱支架（parter）、裸金属支架（每组12枚）。每只猪冠状动脉前降支、回旋支、右冠状动脉各植入一枚支架，术后给予抗血小板药物，12周后复查冠状动脉造影（QCA）分析管腔变化、组织病理、血常规、生化结果，免疫组化检测支架处血管VEGF，ICAM-1，α-actin的变化。结果各组支架植入顺利，12周内无死亡，血管损伤积分无差异，管腔内均无血栓形成。裸支架组支架部位血管腔面积（3．76±0．61）mm^2、最小管腔内径（2．15±0．18）mm小于TES组[（5．13±0．46）mm^2，（2．65±0．21）mm]和DES组[（5．01±0．54）mm^2，（2．65±0．25）mm，P〈0．01]；裸支架内增生内膜面积及内膜增生程度裸支架组大于TES组和乐普支架组（P〈0．05），裸支架组支架部位血管内膜VEGF，ICAM-1，α-actin表达明显强于TES和乐普支架组。支架植入前后各组动物血细胞计数和肝。肾功能无明显变化。结论雷公藤内酯醇洗脱支架能抑制血管新生内膜增殖和炎性因子的表达，在支架植入12周后能有效地预防再狭窄。

Objective To observe the effect of a triptolide-elufing stent （TES） on neointimal hyperplasia in response to vascular injury, inflammation and safety to prevent restenosis after angioplasty. Method Twelve pigs were randomly divided into three groups and received either a bare metal stent （BMS）, a simlimus-eluting stent （SES） or a TES. Each pig was treated with antiplatelet drugs after angioplasty. Biochemistry, vascular morphometry,histopathology and immunohistochemistry were analyzed at 12 weeks after angioplasty. Results The injury scores of the blood vessel were similar in all three groups. There were no differences in minimal lumen diameter or lumen area between the TES [ （ 5.13 ± 0.46 ） mm^2 ; （2.65 ± 0.21 ）mm ] and SES [ （ 5.01 ± 0.54） mm^2 ; （ 2.65 ± 0.25） mm] groups, but they were significantly （P 〈 0.01） larger than those in the BMS group [（3.76± 0.61） mm^2 ; （2.15 ± 0.18） mm]. The neointimal area in the TES group was smaller than that in the BMS group, but was similar to that in the SES group. The expression of VEGF, ICAM-1 and α-actinin were significantly lower in the TES group than in the BMS group. In all groups, the proliferation on both edges of the stents was insignificant. No toxicity was found in the TES group. Conclusions TES inhibits neointimal proliferation and the expression of inflammatory factors in pigs. In this study,TES safely and effectively prevented restenosis for 12 weeks.