川芎嗪药物涂层支架预防猪冠状动脉再狭窄的实验研究

目的 探讨川芎嗪药物涂层支架(TES)预防冠状动脉再狭窄的作用机制及其有效性.方法 TES为金属管状支架经喷涂川芎嗪单体制成(含川芎嗪200μg).采用随机、双盲实验在14只小型猪的冠状动脉左前降支分别置入TES及金属裸支架(BMS)(实验组7只,对照组7只).支架置入前后均行定量冠状动脉造影(QCA)及血管内超声(IVUS)检查.术后第28天随访行QCA及ⅣUS观察支架内膜增殖及血栓形成情况.实验终点处死动物,获取支架置入段血管及支架前后5 cm处组织行病理学及免疫组化检查.结果 14只动物均成功置入支架,4只动物因手术意外死亡未列入统计.5只动物于左前降支置入TES,5只动物置入BMs.术后第28天随访,QCA检查支架段血管直径狭窄百分比两组分别为实验组(10.0±2.1)%和对照组(60.2±23.5)%(P=0.01).IVUS检查显示,两组支架内面积相似,均未见血栓形成.对照组内弹力膜面积较实验组明显减小(P=0.021),而新生内膜面积明显增大(P=0.004).术后处死动物组织形态学检查显示两组血管损伤评分和支架内面积相近(P>0.05),均无明显的炎症反应,但实验组管腔面积(4.34±0.93)mm2]较对照组(1.29±1.02)mm2]明显增加(P=0.011),新生内膜面积(1.51±0.45)mm2]较对照组(4.60±1.39)mm2]明显减少(P=0.004).组织病理学检查提示所有支架置入节段均完全内皮化,实验组增殖细胞核抗原染色阳性细胞核明显减少,凋亡细胞较对照组增多.结论 川芎嗪药物涂层支架能有效抑制血管内膜增殖及血栓形成,减少支架内再狭窄.

The efficacy of tetramethylpyrazine-eluting stents on inhibiting neointima formation in porcine coronary arteries

Objective The aim of this study was to investigate the mechanism and efficacy of tetramethylpyrazine-eluting stents (TES) on inhibiting neointima formation in porcine coronary artefies.Methods TES was prepared by tetramethylpyrazine spray-coated in bare metal stents(BMS).Pigs were implanted with TES or BMS(n=7 each),respectively.Quantitative coronary angiography(QCA)and intravascular ultrasound (IVUS) were performed before,immediately after stenting and at 28 days after stenting.Coronary arteries segments (5 cm) before and post stenting area (5 cm) as well as at stenting location were harvested at 28 days post stenting for histopathological examinations(inflammation,vascular smooth muscle cells proliferation and apoptosis).Results Follow up QCA at 28 days showed that percentage diameter stenosis were significandy lower in the,TES group than that in the BMS group(10.0±2.1)%VS (60.2±23.5)%.P=0.01].Tlle lumen area determined by IVUS was similar between the two groups and there was no in-stent thrombosis in TES or BMS treated animals.Internal elastic lamina area was significantly largerwhile the neointimal ares (1.51±0.45)mm2 vs(4.60±1.39)mm2,P=0.04] Was significantly smaller in the TES group than that in the BMS group.Histopathologieal assessments showed fewer inflammatory cells in the stented-coronary artery walls than those at the border zones of stenting in both groups.The number of proliferating cells were significantly decreased while apoptotic cells were significantly increased in the TES group compared with the BMS group (all P<0.05).Conclusion TES could effectively reduce in.stent restenosis in this porcine model by attenuating Vascular smooth muscle proliferation and enhancing vascular smooth muscle apoptosis post stenting.