Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
Chin Med J (Engl). 2010 Sep;123(17):2405-9.
Coronary artery in-stent restenosis (ISR) and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin (IL)-1β.
Mini pigs (n = 12; 2-3 months old and weighing 25-30 kg) were subjected to thoracotomy. Segments (10 mm) of the mid left anterior descending coronary artery and left circumflex coronary artery were exposed and aseptically wrapped with a cotton mesh soaked with IL-1β (5 µg). After 2 weeks, the animals were anesthetized and quantitative coronary arteriography (QCA) was performed. The stenosis sites were randomized into three groups for stent insertion: a sirolimus-eluting stent (SES) group (Firebird(TM), n = 7), a paclitaxel-eluting stent (PES) group (TAXUS(TM), n = 9), and a bare-metal stent (BMS) group (YINYITM, Dalian Yinyi Biomaterials Development Co., Ltd, China, n = 8). The three different stents were randomly implanted into stenosis segments. Expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), P-selectin and vascular cell adhesion molecule-1 (VCAM-1) was determined by reverse transcription-coupled polymerase chain reaction (RT-PCR).
QCA showed severe stenosis in IL-1β treated segments. The SES and PES groups showed lower 1-month angiographic late lumen loss (LLL) within the stent and the lesion compared with BMS (P < 0.05) by follow-up QCA. The SES showed lower LLL than that of PES in reducing 1-month inflammation lesions in pigs by follow-up QCA ((0.15 ± 0.06) mm vs. (0.33 ± 0.01) mm, P < 0.0001). The neointimal hyperplasia areas in SES and PES showed lower than those of BMS (SES (11.6 ± 1.7) mm(2), PES (27.2 ± 1.6) mm(2) vs. BMS (76.2 ± 1.3) mm(2), P < 0.0001). The mRNA expression of MCP-1 by RT-PCR in SES and PES showed lower than that of BMS at 30 days after stenting (SES 0.20 ± 0.03, PES 0.48 ± 0.49 vs. BMS 0.58 ± 0.07, P < 0.05). Levels of VCAM-1 in SES were significantly lower than those of PES and BMS (SES 0.35 ± 0.08 vs. PES 0.65 ± 0.13, BMS 0.70 ± 0.06, P < 0.05). Histochemical immunostaining of vessel walls showed lower inflammatory chemokine MCP-1 expression in the SES and PES groups compared with BMS.
SESs were superior in reducing 1-month angiographic LLL in inflammation lesions in pigs, strongly suggesting that SESs can suppress inflammatory reactions in ISR at multiple points.
冠状动脉支架内再狭窄（ISR）和晚期支架内血栓仍然是支架置入的重要并发症。白细胞介素（IL）-1β诱导的狭窄猪模型中，研究了西罗莫司和紫杉醇洗脱支架的炎症反应。
对 12 只（2-3 个月大，体重 25-30 公斤）小型猪进行开胸手术。暴露中段左前降支和左旋支冠状动脉的 10mm 节段，用 IL-1β（5μg）浸泡的棉网无菌包裹。2 周后，对动物进行麻醉并进行定量冠状动脉造影（QCA）。将狭窄部位随机分为三组进行支架置入：西罗莫司洗脱支架（SES）组（Firebird（TM），n=7）、紫杉醇洗脱支架（PES）组（TAXUS（TM），n=9）和裸金属支架（BMS）组（YINYI，大连银亿生物材料发展有限公司，中国，n=8）。将三种不同的支架随机植入狭窄部位。通过逆转录-聚合酶链反应（RT-PCR）测定单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）、P-选择素和血管细胞黏附分子-1（VCAM-1）的表达。
QCA 显示 IL-1β处理的节段有严重狭窄。SES 和 PES 组在支架内和病变处的 1 个月时的血管造影晚期管腔丢失（LLL）低于 BMS（P < 0.05），通过随访 QCA 显示。SES 在降低 1 个月时炎症病变中的 LLL 方面优于 PES（0.15±0.06mm 对 0.33±0.01mm，P < 0.0001）。SES 和 PES 的新生内膜增生面积均低于 BMS（SES（11.6±1.7）mm（2），PES（27.2±1.6）mm（2）对 BMS（76.2±1.3）mm（2），P < 0.0001）。SES 和 PES 的 MCP-1 的 RT-PCR 显示在支架置入后 30 天的 mRNA 表达低于 BMS（SES 0.20±0.03，PES 0.48±0.49 对 BMS 0.58±0.07，P < 0.05）。SES 的 VCAM-1 水平明显低于 PES 和 BMS（SES 0.35±0.08 对 PES 0.65±0.13，BMS 0.70±0.06，P < 0.05）。血管壁的组织化学免疫染色显示 SES 和 PES 组的炎症趋化因子 MCP-1 表达低于 BMS。
SES 在降低炎症病变中 1 个月时的血管造影 LLL 方面优于 BMS，这强烈表明 SES 可在多个点抑制 ISR 的炎症反应。
