摘要
Background 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.Methods 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 （FirebirdTM, n=7）, a paclitaxel-eluting stent （PES） group （TAXUSTM, 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）.Results 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） mm2, PES （27.2±1.6） mm2 vs. BMS （76.2±1.3） mm2, 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.Conclusion 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.
Background 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.Methods 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 （FirebirdTM, n=7）, a paclitaxel-eluting stent （PES） group （TAXUSTM, 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）.Results 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） mm2, PES （27.2±1.6） mm2 vs. BMS （76.2±1.3） mm2, 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.Conclusion 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.
