雷帕霉素与紫杉醇药物洗脱支架对小型猪早期冠状动脉炎症性狭窄治疗的定量冠状动脉造影研究

Quantitative Angiographic Results of Sirolimus and Paclitaxel Coated Stents on Inflammatory Coronary Lesions in Pigs

目的:制作小型猪冠状动脉炎症型支架再狭窄模型,用定量冠状动脉造影、测定支架处血管壁内膜增生程度及炎症因子表达等方法探讨雷帕霉素及紫杉醇涂层支架对炎症性冠状动脉狭窄的抑制作用。方法:小型雄性家猪14头,开胸法将冠状动脉外膜包裹吸附白介素-1β(IL-1β)琼脂糖微粒悬液的纸巾。2周后,用定量冠状动脉造影观察管腔狭窄程度及随机分为雷帕霉素支架组(n=7)、紫杉醇支架组(n=9)及裸支架组(n=8)。1个月后进行随访定量冠状动脉造影测定各组冠状动脉支架节段内和支架内的最小管腔直径(MDL),参照管腔直径(RLD),管腔狭窄百分比(DS),计算出晚期管腔丢失(LLL)进行对比分析。塑料包埋法进行支架血管切片,测定管腔增生面积及血管壁单核细胞趋化因子-1(MCP-1)、肿瘤坏死因子-α(TNF-α)、P-选择素、血管细胞间黏附因子-1(VCAM-1)的表达。结果:冠状动脉外膜包裹IL-1β血管段局限性狭窄平均达到70％以上。裸支架组中冠状动脉支架节段内和支架内的LLL明显高于雷帕霉素支架组和紫杉醇支架组,且再狭窄(DS)率高。雷帕霉素支架组及紫杉醇支架组冠状动脉支架节段内和支架内LLL均低于裸支架组,且明显抑制内膜增生(P<0．01)。但只有雷帕霉素支架组明显下调MCP-1,TNF-α,P-选择素和VCAM-1的表达。结论:雷帕霉素和紫杉醇药物洗脱支架对IL-1β诱发的小型猪冠状动脉炎症性狭窄均有较好的抗内膜增殖作用,但在LLL指标及抑制内膜增生方面雷帕霉素优于紫杉醇药物洗脱支架,有可能是通过直接或间接抗炎机制达到的。

Objective ： To investigate the anti-inflammation effects of rapamycin versus paclitaxel coated stents on interleukin-1β induced coronary stenosis in pigs. Methods： Fourteen male domestic young pigs （2 to 3 months, 25 to 30 kg）were operated on via thoracotomy. The mid left anterior descending（LAD） and left circumflex coronary artery （LCx） were respectively undermined 10 mm segment and aseptically wrapped with cotton mesh soaked in IL-1β 5 ug. Two weeks later, the animals were anesthetized and quantitative coronary arteriography （QCA） was performed. The stented coronary artery segments were processed for plastic embedding and HE staining. The intimal areas of the coronary artery were calculated. The expression of MCP-1 ,TNFα ,P-selectin, and VCAM-1 mRNA on the wall of stented vessels were detected by RT-PCR method. Results： The QCA results showed severe stenosis at IL-1β treated LAD and LCx sites. All the stenosis sites were randomized into 3 groups ： sirolimus eluting stent group （ SES, n = 7 ）, paclitaxel eluting stent group （ PES, n = 9） and bare-metal YinyiTM stent （BMS） group （ BMS,n = 8）. Four weeks after PCI, follow-up QCA was performed again. The results showed that compared with BMS, both sirolimus and paclitaxel coated stents reduced a one-month angiographic late lumen loss （LLL） within the stent and the lesion. A significant neointimal hyperplasia in BMS was found. The area of neointimal hyperplasia was markedly inhibited by drugelutingstents （SES 11.6±1.7, PES27.2±1.6% vs BMS76.2±1.3%,P〈0.01）. The mRNA level of MCP-1, TNFα,P-seleetin, and VCAM-I were markedly decreased in SES group compared with PES and BMS groups. Conclusion： Both SES and PES reduced a one-month angiographie LLL and neointima hyperplasia in young pigs. SES was better than PES in LLL. The possible anti-hyperplasia mechanisms of SES in this ISR model may be partly via anti-inflammation effects of SES ,which were not found in PES group.