药物洗脱血管支架研究
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摘要
经皮冠状动脉成形术以及支架植入术后的再狭窄是当前世界上心血管疾病介入治疗领域内的一个主要难题。目前临床上广泛应用的雷帕霉素和紫杉醇洗脱支架仍然存在抗凝血性能不足的问题，并且所用的不可降解高分子载体材料在体内的长期放置所导致的结构性能变化也可能引发相关的临床并发症。针对上述问题，本论文以具备可控降解行为的生物降解高分子材料作为药物释放载体，发展既含有抗增生药物又含有抗凝血药物的涂层材料，研制既具有抗增生又具有抗凝血作用的药物洗脱支架：依据一些中药提纯物具有抗增生和抗凝血的综合特性，本论文也开展了中药提纯药物应用于药物洗脱支架的探索性研究。
依据药物的控释需求、材料的降解行为以及生物材料的临床准入性，粘均分子量为95800的乙交酯-丙交酯共聚物(PLGA)被确定为本论文中血管支架的药物载体材料。抗增生药物雷帕霉素和紫杉醇、抗凝血性药物肝素以及中药提纯药物姜黄素、大黄素被选定为本论文的药物研究对象。利用超声雾化喷涂方法分别制备了五种含单一药物(雷帕霉素、紫杉醇、肝素、姜黄素、大黄素)以及三种含混合药物(雷帕霉素／肝素、雷帕霉素／姜黄素以及姜黄素／肝素)的药物洗脱血管支架。
药物洗脱血管支架撑开前后表面形貌的对比研究表明：涂层均匀连续完整，无交联，AFM测量的平均粗糙度小于1nm，药物洗脱支架装配到3.0×20mm的血管成型球囊上后撑开，涂层没有剥落和裂纹，显示出与不锈钢基底良好的结合力。傅立叶变换红外光谱和X射线光电子能谱的结果均表明药物的吸收峰在药物洗脱薄膜中没有发生移动。
药物洗脱支架的体外药物释放行为研究表明，不同的药物具有不同的释放行为，姜黄素和大黄素在测量的时间范围内呈现出较好的近似零级释放行为，但是姜黄素的释放速度大于大黄素的释放速度，如载药量为20％的支架，姜黄的释放速度为7.37μg／天，而大黄素为4.9μg／天，释放速度的不同导致了释放周期的差别；雷帕霉素的释放行为存在2天的突释期，并且药物含量越大，突释越明显，突释量达到4.7％—20％，突释后的释放呈现出较好的近似零级释放关系；肝素洗脱支架没有突释，整个释放过程呈现出近似零级释放关系，混合药物洗脱(雷帕霉素／肝素，姜黄素／肝素)支架中肝素的释放行为呈现出较好的零级释放行为，但是雷帕霉素和姜黄素的释放行为与单一药物洗脱支架的差别不大，只是释放速度不一样；载药量对释放速度具有比较明显的影响，载药量越大，释放速度越快，但是释放速度的增加比例与药物／高分子的比例的增加不一致。在雷帕霉素支架表面制备PLGA20000控制释放层，可以基本消除雷帕霉素的突释效应，并且延长药物的释放周期。
综合静态血小板吸附，部分凝血活酶时间，纤维蛋白原吸附以及GMP140释放评价实验结果，与不锈钢和纯PLGA的支架涂层相比较，分别载有肝素和姜黄素的PLGA支架涂层都具有良好的抗凝血性，而载有雷帕霉素的PLGA支架涂层具有一定的抗凝血性。在雷帕霉素药物洗脱支架中加入姜黄素可以提高雷帕霉素药物洗脱支架的抗凝血性，在姜黄素洗脱支架涂层中加入肝素可以进一步提高其抗凝血性能，这为研制同时具有抗增生和抗凝血功能的药物洗脱支架奠定了很好的基础。
LDH，Alamar Blue~(TM)以及细胞染色等细胞生物学评价结果为：与不锈钢相比，包覆雷帕霉素，姜黄素以及肝素涂层的PLGA都具有抑制平滑肌细胞生长和增殖的作用，其中抑制作用的有效性排序为雷帕霉素＞姜黄素＞肝素，并随着载体材料中药物浓度的增加，抑制平滑肌细胞增生的作用越明显。
Currently, restenosis after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation is the major difficult problem of the field of cardiovascular intervention therapy in the world. The anticoagulation of clinical rapamycin and paclitaxel eluting stents is still deficient; furthermore, the long-standing nonbiodegradable polymer drug carrier in human body may also bring many clinical complications because of the change of its structure and properties. To above questions, this study aimed at developing a novel drug-eluting stent with a biodegradable polymer coating which contained not only antiproliferative drug but anticoagulation drug. Considering the good anticoagulation and anti-proliferation of some Chinese herbal drug, this paper carried out some exploring studies of these drugs eluting stentsAccording to the controlled release requirements, biodegradable behavior and the clinical admittance of biodegradable biomaterials, the PLGA (poly lactide-co-glycoide) (Its average-viscosity molecular weight was 95800, LA/GA=85/15) was chosen as the drug carrier in this paper. Anti-proliferative drug including rapamycin and paclitaxel, anticoagulation drug such as heparin and Chinese herbal drug including curcumin and emodin were investigated. Five single drug-eluting stents (rapamycin, paclitaxel, curcumin, emodin and heparin) and three mixing-drug eluting stents (rapamycin-heparin, curcumin-heparin and rapamycin-curcumin) were prepared using ultrasonic atomization spray method.The comparative results of pre- and post-dilation morphology of drug eluting stents indicated that the coating was very smooth, uniform and integrated. There were no webbings and "bridges" between struts. The avergae roughness of coating measured by atomic force microscopy (AFM) was below 1nm. The drug-eluting stents were mounted onto a angioplasty balloon (3.0×20mm) and then dilated, the coating did not peel and crack, suggesting that the coating had the ability to withstand the compressive and tensile strains imparted during this process. The results of Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) indicated that there was no peak shift for drug in drug-eluting PLGA films.
The results of in vitro drug release profile from stents indicated that different drug had different release behavior. The release profile of curcumin and emodin from stents exhibited approximate zero-order release profile, however, the release rate of curcumin was larger than emodin, for example, the curcumin-eluting stent which contained 20wt% curcumin was 7.37μg/day and that of emodin was 4.9μg/day, the different release rate resulted in different release period. The release behavior of rapamycin from stent had a two phase release profile with a burst release within 2 days, the burst release changed from 4.7% to 20% with the increase of drug content from 15% to 40%, after initial burst release (2 days) followed by a longer lasting, slower sustained release, the decreased release phase appeared to a approximate zero-order release model. The heparin release from heparin-eluting stents had an approximate zero-order release profile without burst release and the heparin release of rapamycin-heparin and curcumin-heparin eluting stents exhibited good zero-order profile, however, the release behavior of rapamycin and curcumin was similar with corresponding single drug-eluting stents and the release rate was different. The drug content influenced the release rate significantly and the release rate increased with the increase of drug content but was not proportional to ratio of drug-polymer. The control release layer prepared from PLGA20000 onto single rapamycin-eluting stent surface can eliminate the burst release of rapamycin and prolong the release period of rapamycin.
In this study, platelet adhesion and activation (GMP140, P-selection), activated partial thromboplastin time (APTT) and fibrinogen adsorption were used to characterize the blood compatibility of drug-eluting stent. Compared with stainless steel and single PLGA coating stent, the heparin and curcumin eluting stents had a good hemocompatibility, however, the blood compatibility of rapamycin-eluting stent was deficient. Incorporating curcumin in rapamycin-eluting stents can improve the anticoagulation of rapamycin-eluting stent. Loading heparin in curcumin-eluting stent further enhanced the anticoagulation of curcumin-eluting stent. This established good base for developing drug-eluting stents which had not only good anticoagulation but also anti-proliferation.
The biological evaluation results of LDH, Alamar Blue~(TM) and cell staining indicated that three kinds of drug-loaded films, including rapamycin, curcumin, heparin loading PLGA films, all can inhibit smooth muscle cell grow and proliferate compared with stainless steel and PLGA. The order of effect was rapamycin＞curcumin＞heparin. The anti-proliferation effect improved with the increase of drug content.
依据药物的控释需求、材料的降解行为以及生物材料的临床准入性，粘均分子量为95800的乙交酯-丙交酯共聚物(PLGA)被确定为本论文中血管支架的药物载体材料。抗增生药物雷帕霉素和紫杉醇、抗凝血性药物肝素以及中药提纯药物姜黄素、大黄素被选定为本论文的药物研究对象。利用超声雾化喷涂方法分别制备了五种含单一药物(雷帕霉素、紫杉醇、肝素、姜黄素、大黄素)以及三种含混合药物(雷帕霉素／肝素、雷帕霉素／姜黄素以及姜黄素／肝素)的药物洗脱血管支架。
药物洗脱血管支架撑开前后表面形貌的对比研究表明：涂层均匀连续完整，无交联，AFM测量的平均粗糙度小于1nm，药物洗脱支架装配到3.0×20mm的血管成型球囊上后撑开，涂层没有剥落和裂纹，显示出与不锈钢基底良好的结合力。傅立叶变换红外光谱和X射线光电子能谱的结果均表明药物的吸收峰在药物洗脱薄膜中没有发生移动。
药物洗脱支架的体外药物释放行为研究表明，不同的药物具有不同的释放行为，姜黄素和大黄素在测量的时间范围内呈现出较好的近似零级释放行为，但是姜黄素的释放速度大于大黄素的释放速度，如载药量为20％的支架，姜黄的释放速度为7.37μg／天，而大黄素为4.9μg／天，释放速度的不同导致了释放周期的差别；雷帕霉素的释放行为存在2天的突释期，并且药物含量越大，突释越明显，突释量达到4.7％—20％，突释后的释放呈现出较好的近似零级释放关系；肝素洗脱支架没有突释，整个释放过程呈现出近似零级释放关系，混合药物洗脱(雷帕霉素／肝素，姜黄素／肝素)支架中肝素的释放行为呈现出较好的零级释放行为，但是雷帕霉素和姜黄素的释放行为与单一药物洗脱支架的差别不大，只是释放速度不一样；载药量对释放速度具有比较明显的影响，载药量越大，释放速度越快，但是释放速度的增加比例与药物／高分子的比例的增加不一致。在雷帕霉素支架表面制备PLGA20000控制释放层，可以基本消除雷帕霉素的突释效应，并且延长药物的释放周期。
综合静态血小板吸附，部分凝血活酶时间，纤维蛋白原吸附以及GMP140释放评价实验结果，与不锈钢和纯PLGA的支架涂层相比较，分别载有肝素和姜黄素的PLGA支架涂层都具有良好的抗凝血性，而载有雷帕霉素的PLGA支架涂层具有一定的抗凝血性。在雷帕霉素药物洗脱支架中加入姜黄素可以提高雷帕霉素药物洗脱支架的抗凝血性，在姜黄素洗脱支架涂层中加入肝素可以进一步提高其抗凝血性能，这为研制同时具有抗增生和抗凝血功能的药物洗脱支架奠定了很好的基础。
LDH，Alamar Blue~(TM)以及细胞染色等细胞生物学评价结果为：与不锈钢相比，包覆雷帕霉素，姜黄素以及肝素涂层的PLGA都具有抑制平滑肌细胞生长和增殖的作用，其中抑制作用的有效性排序为雷帕霉素＞姜黄素＞肝素，并随着载体材料中药物浓度的增加，抑制平滑肌细胞增生的作用越明显。
Currently, restenosis after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation is the major difficult problem of the field of cardiovascular intervention therapy in the world. The anticoagulation of clinical rapamycin and paclitaxel eluting stents is still deficient; furthermore, the long-standing nonbiodegradable polymer drug carrier in human body may also bring many clinical complications because of the change of its structure and properties. To above questions, this study aimed at developing a novel drug-eluting stent with a biodegradable polymer coating which contained not only antiproliferative drug but anticoagulation drug. Considering the good anticoagulation and anti-proliferation of some Chinese herbal drug, this paper carried out some exploring studies of these drugs eluting stentsAccording to the controlled release requirements, biodegradable behavior and the clinical admittance of biodegradable biomaterials, the PLGA (poly lactide-co-glycoide) (Its average-viscosity molecular weight was 95800, LA/GA=85/15) was chosen as the drug carrier in this paper. Anti-proliferative drug including rapamycin and paclitaxel, anticoagulation drug such as heparin and Chinese herbal drug including curcumin and emodin were investigated. Five single drug-eluting stents (rapamycin, paclitaxel, curcumin, emodin and heparin) and three mixing-drug eluting stents (rapamycin-heparin, curcumin-heparin and rapamycin-curcumin) were prepared using ultrasonic atomization spray method.The comparative results of pre- and post-dilation morphology of drug eluting stents indicated that the coating was very smooth, uniform and integrated. There were no webbings and "bridges" between struts. The avergae roughness of coating measured by atomic force microscopy (AFM) was below 1nm. The drug-eluting stents were mounted onto a angioplasty balloon (3.0×20mm) and then dilated, the coating did not peel and crack, suggesting that the coating had the ability to withstand the compressive and tensile strains imparted during this process. The results of Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) indicated that there was no peak shift for drug in drug-eluting PLGA films.
The results of in vitro drug release profile from stents indicated that different drug had different release behavior. The release profile of curcumin and emodin from stents exhibited approximate zero-order release profile, however, the release rate of curcumin was larger than emodin, for example, the curcumin-eluting stent which contained 20wt% curcumin was 7.37μg/day and that of emodin was 4.9μg/day, the different release rate resulted in different release period. The release behavior of rapamycin from stent had a two phase release profile with a burst release within 2 days, the burst release changed from 4.7% to 20% with the increase of drug content from 15% to 40%, after initial burst release (2 days) followed by a longer lasting, slower sustained release, the decreased release phase appeared to a approximate zero-order release model. The heparin release from heparin-eluting stents had an approximate zero-order release profile without burst release and the heparin release of rapamycin-heparin and curcumin-heparin eluting stents exhibited good zero-order profile, however, the release behavior of rapamycin and curcumin was similar with corresponding single drug-eluting stents and the release rate was different. The drug content influenced the release rate significantly and the release rate increased with the increase of drug content but was not proportional to ratio of drug-polymer. The control release layer prepared from PLGA20000 onto single rapamycin-eluting stent surface can eliminate the burst release of rapamycin and prolong the release period of rapamycin.
In this study, platelet adhesion and activation (GMP140, P-selection), activated partial thromboplastin time (APTT) and fibrinogen adsorption were used to characterize the blood compatibility of drug-eluting stent. Compared with stainless steel and single PLGA coating stent, the heparin and curcumin eluting stents had a good hemocompatibility, however, the blood compatibility of rapamycin-eluting stent was deficient. Incorporating curcumin in rapamycin-eluting stents can improve the anticoagulation of rapamycin-eluting stent. Loading heparin in curcumin-eluting stent further enhanced the anticoagulation of curcumin-eluting stent. This established good base for developing drug-eluting stents which had not only good anticoagulation but also anti-proliferation.
The biological evaluation results of LDH, Alamar Blue~(TM) and cell staining indicated that three kinds of drug-loaded films, including rapamycin, curcumin, heparin loading PLGA films, all can inhibit smooth muscle cell grow and proliferate compared with stainless steel and PLGA. The order of effect was rapamycin＞curcumin＞heparin. The anti-proliferation effect improved with the increase of drug content.
引文
[1] Ankur Raval, Animesh Choubey, Chhaya Engineer, et al. Development and assessment of 316LVM cardiovascular stents. Materials Science and Enginering A 2004; 386:331-343
[2] 奚廷斐. 生物材料进展(二). 生物医学工程与临床 2004; 8(4): 244-248
[3] E Regar, G Sianos, P W Serruys. Stent development and local drug delivery. British Medical Bulletin 2001 ;59: 227-248
[4] Teirstein P.S, Massullo V, Jani S, et al. Three-year clinical and angiographic follow-up after intracoronary radiation: Results of a randomized clinical trial. Circulation 2000; 101:360-365
[5] Monnink SH, van Boven AJ, Peels HO, et al. Silicon-carbide coated coronary stents have low platelet and leukocyte adhesion during platelet activation. J Investig Med 1999; 47:304-310
[6] K. Gutensohn, C. Beythien, J. Bau, et al. In vitro analyses of diamond-like carbon coated stents: Reduction of metal ion release, platelet activation, and thrombogenicity. Thrombosis Research 2000; 99: 577-585
[7] Aude M, Erbel R, Issa H, Meyer J. Quantitative analysis of elastic recoil after balloon angioplasty and after intracoronary implantation of balloon-expandable Palmaz-Schatz stents. Am J Cardiol 1987; 60: 20B-28B
[8] Lowe HC, Oesterle SN, Khachigian LM. Coronary in-stent restenosis: current status and future strategies. J Am Coll Cardiol 2002; 39(2): 183-193
[9] Hoffmann R, Mintz GS, Dussaillant GR, et al. Patterns and mechanism of in-stent restenosis. A serial intravascular ultrasound study. Circulation 1996; 94(6): 1247-1254
[10] Grewe P.H, Deneke T, Machraoui A. et al. Acute and chronic tissue response to coronary stent implantation: pathologic findings in human specimen. J Am Coll Cardiol 2000; 35: 157-163
[11] Robert S. Schwartz. Pathophysiology of restenosis: interaction of thrombosis, hyperplasia and/or remodeling. The American Journal of Cardiology 1998; 81(7A): 14E-17E
[12] Rekhter M.D, O'Brien E, Shah N et al. The importance of thrombus organization and stellate cell phenotype in collagen I gene expression in human, coronary atherosclerotic and restenotic lesions. Cardiovasc Res 1996; 32: 496-502
[13] 赵革平，沃兴德，洪行德，刘德文．姜黄醇提取物对血管平滑肌细胞增殖的影响．浙江中医学院学报 1997：23(3)：21-23
[14] Bauters C, de Groote P, Adamantidis M, et al. Proto-oncogene expression in rabbit aorta after wall injury. First marker of the cellular process leading to restenosis after angioplasty?. Eur Heart J 1992; 13:556-559
[15] Moreno P. R, Palacios I. F, Leon M. N. et al. Histopathologic comparison of human coronary in-stent and post-balloon angioplasty restenotic tissue. Am J Cardiol 1999; 84:462-466
[16] Farb A, Sangiorgi G, Carter A. J. et al. Pathology of acute and chronic coronary stenting in humans. Circulation 1999; 99:44-52
[17] Baurschmidt P, Schaldach M. Electrochemical aspects of the thrombogenicity of a materials. Journal of Bioengineering 1997; 1(11): 261-267
[18] Bartorelli AL, Trabattoni D, Montorsi P, et al. Aspirin alone antiplatelet regimen after intracoronary placement of Carbostent: the ANTARES study. Catheter Cardiovasc Interv 2002; 55:150-156
[19] Antoniucci D, Bartorelli A, Vaenti R, et al. Clinical and angiographic outcome after coronary artery stenting with the Carbostent. Am J Cardiol 2000; 85: 821-825.
[20] Antoniucci D, Vaenti R, Migliorini A, et al. Clinical and angiographic outcomes following elective implantation of Carbostent in patients at high risk of restenosis and target vessel failure. Cathet Cardiovasc Interv 2001; 54:420-426
[21] Van der Giessen W, van Beusekom HM, Hofma SH et al. Preliminary results with bi-component metal-biodegradable polymer stents in porcine coronary mode. Eur Heart J 1996;17:178
[22] Lewis AL. Phosphorylcholine-based polymers and their use in the prevention of biofouling. Coll Surf B 2000; 18:261-275
[23] AL Lewis, LA Tolhurst, PW Stratford. Analysis of a phosphorylcholine-based polymer coating on a coronary stent pre- and post-implantation. Biomaterials 2002; 23:1697-1706
[24] AL Lewis, Zoie L, Cumming Hind, H. Goreish et al. Crosslinkable coatings from phosphorylcholine-based polymers. Biomaterials 2001;22:99-111
[25] Toutouzas K, Stefanadis C, Tsiamis E et al. Effects of stents coated by an autologous vein graft on intima hyperplasia in porcine coronary arteries. J Am Coll Cardiol 1998;31:414-421
[26] Toutouzas K, Stefanadis C, Tsiamis E et al. Autologous vein-graft covered steut for the treatment of coronary artery disease:immediate and long-term results. Eur Heart J 1998;19:498-505
[27] 潘长江，王进，黄楠．血管支架内再狭窄的研究进展．中国生物医学工程学学报 2004；23(2)：152-156
[28] Elezi S, Kastrati A, Neumann F. J. et al. Vessel size and long-term outcome after coronary stent placement. Circulation 1998; 98:1875-1880
[29] Sousa JE, Serruys PW, Costa MA. New frontiers in cardiology: drug-eluting stents: Part 1. Circulation 2003; 107:2274-2279
[30] Samer M. Garas, Philip Huber, Neal A. Scott. Overview of therapies for prevention of restenosis after coronary interventions. Pharmacology & Therapeutics 2001; 92:165-178
[31] Kjeld Christensen, Roll Larsson, Hakan Emanuelsson et al. Heparin coating of the stent graft-effects on platelets, coagulation and complement activation. Biomaterials 2001; 22:349-355
[32] Young Keun Ahn, MD, Myung Ho Jeong et al. Preventive effects of the heparin-coated steut on restenosis in the porcine model. Catheterization and Cardiovascular Interventions 1999; 48:324-331
[33] Francis J. Dumont, Qingxiang Su. Mechanism of action of the immunosuppressant rapamycin. Life science 1996; 58(5): 373-395
[34] Klugherz BD, Llanos G, Lieuallen W, et al. Tweuty-eight-day efficacy and pharmacokinetics of the sirolimus-eluting stent. Coron Artery Dis 2002; 13: 183-188
[35] Anand Babu Dhanikula, Ramesh Panchagnula. Localized paclitaxel delivery. International Journal of Pharmaceutica 1999; 183: 85-100
[36] Axel DI, Kunert W, Goggelmann C et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation 1997; 96:636-645
[37] Rowinsky EK, Donehower RC. Paclitaxel(taxol). N Eng J Med 1995; 332(15):1004-1014
[38] K. T. Nguyen, S. -H. Su, A. Sheng, et al. In vitro hemocompatibility studies of drug-loaded poly-(l-lactic acid) fibers. Biomaterials 2003; 24:5191-5201
[39] Kytai T. Nguyen, Nishat Shaikh, Kajal P. Shukla, et al. Molecular responses of vascular smooth muscle cells and phagocytes to curcumin-eluting bioresorbable stent materials. Biomaterials 2004; 25:5333-5346
[40] 尹春琳，徐成斌．大黄素对血管平滑肌细胞增生抑制作用的机制．北京医科大学学报 1998；30(6)：515-517
[41] Barone GW, Conerly JM, Farley PC. et al. Endothelial injury and vascular dysfunction associated with the Fogarty balloon catheter. J Vasc Surg 1989; 9(3): 422-425
[42] Laitinen M, Hartikainen J, Hiltunen MO, et al. Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. Human Gene Ther 2000; 11(2): 263-270
[43] Neil Swanson, Kai Hogrefe, Qamar Javed, Anthony H. Gershlick. In vitro evaluation of vascular endothelial growth factor (VEGF)-eluting stents. International Journal of Cardiology 2003; 92:265-269
[44] Van der Giesen WJ, Lincoff AM, Schwartz RS, etc. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation 1996; 94(7): 1690-1697
[45] Barend L. Van der Hoeven, Nuno M.M. Piers, Hazem M. Warda, et al. Drug-eluting stents: results, promises and problems. International Journal of Cardiology 2005; 99:9-17
[46] Palmaz JC, Bailey S, Marton D, Sprague E. Influence of stent design and material composition on procedure outcome. J Vasc Surg 2002; 36(5): 1031-1039
[47] Virmani R, Kolodgie FD, Farb A, et al. Drug-eluting stents: are human and animal studies comparable?. Heart 2003; 89(2): 133-138
[48] Long-term effects of stem-based delivery of sirolimus in the porcine model. Am J Cardiol 2002; 90(6A): TCT199
[49] Welt FGP, Rogers C. Inlammation and restenosis in the stent era. Arterioscl Thromb Vasc Biol 2002;22:1769-1776.
[50] Sousa JE, Costa MA, Abizaid A, et al. Two year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation 2003; 107:381-383
[51] Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346(23): 1773-1780
[52] Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents verus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003; 349(14): 1315-1323
[53] Schofer J, Schluter M, Gershlick AH, et al. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomized controlled trial (E-SIRIUS). Lancet 2003; 362(9390): 1093-1099
[54] Curcio A, Torella D, Guda G, et al. Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis. Am J Physiol Heart Circ Physiol 2004; (286): 902-908
[55] Babinska A, Markell MS, Salifu MO, et al. Enhancement of human platelet aggregation and secretion induced by rapamycin. Nephrol Dial Transplant 1998; 13(12): 3153-3159
[56] 周保国，李红梅．黄连素在心血管疾病中的应用研究进展．实用中西医结合杂志 1997；10(7)：609-609
[57] Neil Swanson, Kai Hogrefe, Qamar Javed, et al. In vitro evalution of vascular endothelial growth factor (VEGF)-eluting stents. International Journal of Cardiology 2003; 92:265-269
[58] Barend L. van der Hoeven, Nuno M. M. Pires, Hazem M. Warda, et al. Drug-eluting stents: results, promises and problems. International Journal of Cardiology 2005; 99:9-17
[59] Alt E, Haehnel I, Beilharz C, Prietzel K, et al. Inhibition of neointima formation after experimental coronary artery stenting: a new biodegradable stent coating releasing hirudin and proctacyclin analogue iloprost. Circulation 2000; 101:1453-1458
[60] Samer M. Garas, Philip Huber, Neal A. Scott. Overview of therapies for prevention of restenosis after coronary interventions. Pharmacology & Therapeutics 2001; 92:165-178
[61] Vivek Rajagopal, Stanley G. Rockson. Coronary restenosis: A review of mechanisms and management. The American Journal of Medicine 2003; 115: 547-553
[62] Martin R. Bennett, Michael O'Sullivan. Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy. Phamacology & Therapeutics 2001; 91: 149-166.
[63] Mei-Chin Chen, Hsiang-Fa Liang, Ya-Ling Chiu, et al. A novel drug-eluting stent spray-coated with multi-layers of collagen and sirolimm. Journal of controlled release 2005; 108:178-189
[64] 平其能等编著 现代药剂学 中国医药科技出版社 北京 2001．7第一版
[65] J. Eduardo Soma, Patrick W. Serruys, Marco A. Costa. New frontiers in cardiology: Drug-eluting stems: Part Ⅰ. Circulation 2003; 107:2274-2279
[66] 陈建海主编 药用高分子材料与现代药剂 科学出版社 北京 2003．8第一版
[67] Lens, PFH Harmsen etc. Immobilization of functionalized alkyl-poly(ethylene oxide) surfactants on poly(ethylene) surfaces by means of an argon plasma treatment. J Biomater Sci. Polymer Edn 1997; 18(12): 963-971
[68] Mansoor Amiji, Kinam Park. Surface modification of polymeric biomatedals with poly(ethylene oxide),albumin and heparin for reduced thrombogenieity. J Biomater Sci. Polymer Edn 1993; 4(3): 217-227
[69] Merill EW, Salzman EW. Poly(ethylene oxide) as a biomaterials. Am Soc Artif Intern Organ 1983; 6:60-72
[70] Ron Waksman. Drug-eluting stents: From bench to bed. Cardiovascular Radiation Medicine 2002; 3:226-241
[71] E Regar, G Sianos and P W Serruys. Stent development and local drug delivery. British Medical Bulletin 2001 ;59: 227-248
[72] Shrirang V. Ranade, Kathleen M. Miller, Robert E. Richard, et al. Physical characterization of controlled release of paclitaxel from the TAXUSTM Express2TM drug-eluting stent. J Biomed Mater Res 2004; 71 A: 625-634
[73] Finkelstein A, McClean D, Kar S, et al. Local drug delivery via a coronary stent with programmable release pharmacokinetics. Circulation 2003; 107(5): 777-784
[74] Curcio A, Torella D, Cuda G, et al. Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis. Am J Physiol Heart Circ Physiol 2004; (286):902-908
[75] Virmani R, Kolodgie FD, Farb A, Lafont A. Drug eluting stents: are human and animal studies comparable?. Heart 2003;89(2): 133-138.
[76] Babinska A, Markell MS, Salifu MO, et al. Enhancement of human platelet aggregation and secretion induced by rapamycin. Nephrol Dial Transplant 1998; 13(12): 3153-3159
[77] Willem J. van der Giessen, Heleen M.M. van Beusekom, Rolf Larsson, Patrick W. Serruys. Heparin-coated coronary stents. Current Interventional Cardiology Reports 1999;1: 234-240;
[78] Eli I. Lev, Abid R. Assali, Lgal Teplisky, et al. Comparison of outcomes up to six months of heparin-coated with noncoated stents after percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2004; 93: 741-743
[79] Huang, M. T., Lysz, T., Ferraro, T., Abidi, T. F., Laskin, J. D., & Conney, A. H.. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Research 1991; 51: 813-819
[80] Panchatcharam Manikandan, Miriyala Sumitra , Srinivasan Aishwarya, Bhakthavatsalam Murali Manohar, Beema Lokanadamc, Rengarajulu Puvanakrishnan. Curcumin modulates free radical quenching in myocardial ischaemia in rats. The International Journal of Biochemistry & Cell Biology 2004; 36: 1977-1990;
[81] Kytai T. Nguyen, Nishat Shaikh, Kajal P. Shukla, Shih-Horng Su, Robert C. Eberhart, Liping Tang Molecular responses of vascular smooth muscle cells and phagocytes to curcumin-eluting bioresorbable stent materials. Biomaterials 2004; 25: 5333-5346
[82] Mohan N. Babapulle, Mark J. Eisenberg. Coated stents for the prevention of restenosis: Part II. Circulation 2002; 106: 2859-2866
[83] Samer M. Garas, Philip Huber, Neal A. Scott. Overview of therapies for prevention of restenosis after coronary interventions. Pharmacology & Therapeutics 2001; 92: 165-178
[84] I.De Scheerder, J. Sohier, E. Verbeken, et al. Biocompatibility of coronary stent materials: Effect of electrochemical polishing. Electropolishing 2001; 32: 142-148
[85] De Scheerder I, Verbeken E, Van Humbeeck. Metallic surface modification. Semin Interv Cardiol 1998; 3: 139-144
[86] Tepe G, Wendel HP, Khorchidi S et al. Thrombogenicity of various endovascular stent types: an in vitro evaluation. J vasc Interv Radiol 2002; 13:1029-1035
[87] Palmz JC, Benson A, Sprague EA. Influence of surface topography on endothelialization of intravascular metallic material. J Vasc Interv Radiol 1999; 10:439-444
[88] Van Belle E, Tio FO, Couffinhal T, Maillard L, Passed J, Isner JM. Stent endothelialization. Time course, impact of local catheter delivery, feasibility of recombinant protein administration, and response to cytokine expedition. Circulation 1997;95:438-448
[89] P.W. Heyman, C.S. Cho, J.C. Mcrea, et al. Heparinized polyurethanes: in vitro and in vivo studies. J Biomed Mater Res 1985; 19: 419-436
[90] W.LJ. Himrichs, H.W.M. Ten Hoopen, M.J.B. Wissink, et al. Design of a new type of coating for the controlled release of heparin. Journal of controlled release 1997; 45: 163-176
[91] Camiel C.L Peerlings, Hans H.L.Hanssen, Raymond T.J.Bevers, et al. Heparin release from Slippery-when-wet guides wires for intravascular use. J Biomed Mater Res (Appl Biomater) 2002; 63:692-698
[92] Kjeld Christensen, Rolf Larsson, Hakan Emanuelsson, et al. Improved blood compatibility of a stent graft by combining heparin coating and abciximab. Thrombus Research 2005; 115:245-253
[93] Mingchao shen, etc. PEO-like plasma polymerized tetraglyme surface interactions with leukocytes and proteins: in vitro and in vivo studies. J Biomater Sci. Polymer. Edn. 2002; 13(4):367-375
[94] 许海燕 孔桦 杨子彬 抗凝血高分子材料的研究进展及其在心血管外科中的应用 高分子材料科学与工程 2001；17(5)：167-169
[95] Harry C. Lowe, Stephen N. Oesterle, Levon M. Khachigian. Coronary in-stent restenosis: Current status and future strategies. Journal of the American College of Cardiology 2002; 39(2): 183-193
[96] Bennett MR, O'Sullivan M. Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy. Pharmacol Ther 2001; 91:149-166
[97] Farb A, Sangiorgi G, Carter AJ, et al. Pathology of acute and chronic coronary stenting in humans. Circulation 1999; 99:44-52
[98] Kastrati A, Mehilli J, Dirschinger J, et al. Restenosis after coronary placement of various stent types. Am J Cardiol 2001; 87:34-39
[99] Finkelstein A, McClean D, Kar S, et al. Local drug delivery via a coronary stent with programmable release pharmacokinetics. Circulation 2003; 107:777-784.
[100] Sousa JE, Sousa AG, Costa MA, Abizaid AC, Feres F. Use of rapamycin impregnated stents in coronary arteries. Transplant Proc 2003; 35:S165-S170.
[101] Oberhoff M, Herdeg C, Baumbaeh A, Karsch KR. Stent-based antirestenotic coatings (sirolimus/paclitaxel). Cathet Cardiovasc Interv 2002; 55:404-408
[102] Frank Alexis, Subbu S. Venkatraman, Santosh Kumar Rath, Freddy Boey. In vitro study of release mechanisms of paelitaxel and rapamyein from drug-incorporated biodegradable stent matrices. Journal of controlled release 2004; 98:67-74
[103] 李又欣 冯新德 控制药物释放体系及其机理 高分子学报 1991；19(1)： 19-27
[104] 杨亚楠 尹静波 刘芳 高分子材料在药物控制释放方面的应用 吉林工学院学报 2001：22(3)：38-40
[105] C. W. Hwang, D. Wu, E. R. Edelman. Impact of transport and drug properties on the local pharmacology of drug-eluting stents. International Journal of Cardiovascular Interventions 2003; 5: 7-12
[106] E. C. SIMS, M. T. ROTHMAN, T. D. WARNER, M. E. B. POWELL. Coronary Artery Brachytherapy. Clinical Oncology (2002) 14:313-326
[107] Gordon A. A. Ferns, Tony Y. Avades. The mechanism of coronary restenosis: insights from experimental models. International Journal of Experimental Pathology 2000; 81:63-88
[108] P. B. J. Burton, M. H. Yacoub, P. J. R. Barton, Rapamycin (Sirolimus) inhibits heart cell growth in vitro, Pediatr. Cardiol 1998; 19: 468-470
[109] 尹春琳，徐成斌．芦荟大黄素对动脉损伤后血管平滑肌细胞增殖的影响 中国中西医结合杂志 1998：18(7)：420-422
[110] Dong-Hoon Hahm, Jeong-Min Kim, Jonghoe Byun, et al. Development of a novel drug-coated stent using eurcumin as antiproliferative drug. Poster Abstracts, Cardiovascular Pathology 2004; (13):S80-S138
[111] Ron Waksman. Drug-eluting stents: From bench to bed. Cardiovascular Radiation Medicine 2002; 3:226-241
[112] Shrirang V. Ranade, Kathleen M. Miller, Robert E. Richard, et al. Physical characterization of controlled release of paclitaxel from the TAXUSTM Express2TM drug-eluting stent. J Biomed Mater Res 2004; 71A: 625-634
[113] Felix C. Tanner, Zhi-Yong Yang, Eric Duckers, et al. Expression of Cyclin-dependent kinase inhibitors in vascular disease. Circulation Research 1998; 82:396-403
[114] J. Eduardo Sousa, Patrick W. Serruys, Marco A. Coata. New frontiers in cardiology: drug-eluting stents Part Ⅰ. Circulation 2003; 107:2274-2279
[115] M. Poon, S. O. Marx, R. Gallo, J. J. Badimon, M. B. Taubman, A. R. Marks, Rapamycin inhibits vascular smooth muscle cell migration, J. Clin. Invest 1996; 98:2277-2283
[116] Frank Alexis, Subbu S. Venkatraman, Santosh Kumar Rath, Freddy Boey. In vitro study of release mechanisms of paclitaxel and rapamycin from drug-incorporated biodegradable stent matrices. Journal of Controlled Release 2004; 98: 67-74
[117] Maud B. Gorbet, Michael V. Sefton. Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. Biomaterials 2004; 25:5681-5703
[118] Diran Basmadjian, Michael V, Sefton etc. Coagulation on biomaterials in flowing blood: some theoretical consideration. Biomaterials 1997; 18:1511-1520
[119] 许海燕 孔桦 杨子彬 抗凝血高分子材料的研究进展及其在心血管外科中的应用 高分子材料科学与工程 2001；17(5)：167-171
[120] Alexander Welle, Michael Grunze, Dsidra Tur. Plasma protein adsorption and platelet adhesion on poly[bis(trifluoroethoxy)phosphazene] and reference materials surfaces. Journal of colloid and interface science 1998; 197:263-274
[121] R. J. Green, M. C. Davies, C. J. Roberts, et al. Competitive protein adsorption as observed by surface plasmon resonance. Biomaterials 1999; 20: 385-391
[122] 胡国栋．聚氨酯的血液相容性评价．国外医学生物医学工程分册，2002；25(6)：271-273
[123] 王传华，冷希岗．生物材料诱发血栓形成机制的研究进展．国外医学生物医学工程分册，1998：21(1)：1-5
[124] 王春仁．生物材料表面血浆蛋白的吸附．国外医学生物医学工程分册，1995：18(6)：334-337
[125] 奚廷斐，王春仁，田文华，雷学会．生物材料血液相容性综合评价体系的研究．中国生物医学工程学报，1989：8(4)：212-221
[126] 石晶 吴树荣 姜黄素对大鼠血小板聚集和血栓形成的影响 军医进修学院学报 1996：17(1)：31-33
[127] 沃兴德，崔小强，唐利华．姜黄素对食饵性高脂血症大鼠血浆脂蛋白代谢相关酶活性的影响．中国动脉硬化杂志，2003，11(3)：223-226
[128] Srivastava R, Puri V, Srimal RC, et al. Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. Arzneimittelfors- chung, 1986;36(4): 715-717
[129] Shah BH, Nawaz Z, Pertani SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acidmediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol, 1999;58(7): 1167-1172
[130] Huang, M. T, Lysz, T, Ferraro, T, Abidi, et al. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Research 1991: 51: 813-819
[131] K. T. Nguyen, S. -H. Su, A. Sheng, D. Wawro, et al. In vitro hemocompatibility studies of drug-loaded poly-(l-lactic acid) fibers. Biomaterials 2003; 24:5191-5201
[132] Panchatcharam Manikandan, Midyala Sumitra, Srinivasan Aishwarya, Bhakthavatsalam Murali Manohar, Beema Lokanadamc, Rengarajulu Puvanakrishnan. Curcumin modulates free radical quenching in myocardial ischaemia in rats. The International Journal of Biochemistry & Cell Biology 2004; 36:1977-1990
[133] Babinska A, Markell MS, Salifu MO, et al. Enhancement of human platelet aggregation and secretion induced by rapamycin. Nephrol Dial Transplant 1998; 13(12): 3153-3159
[134] 万征，蔡衡，李晓春等．雷帕霉素药物洗脱支架的临床应用研究．天津医学 2004；32(9)：511-513，，
[135] Yvette B. J. Aldenhoff, Menno L. W. Knetsch, Johannes H. L. Hanssen, Theo Lindhout, et al. Coils and tubes releasing hepadn. Studies on a new vascular graft prototype. Biomaterials 2004; 25:3125-3133
[136] Kjeld Christensen, Rolf Larsson, Hakan Emanuelsson, et al. Improved blood compatibility of a stent graft by combining heparin coating and abciximab. Thrombus Research 2005; 115:245-253
[137] Ubbink-kok T, Anderson JA, Konings WN. Inhibition of electron transfer and uncoupling effects by emodin and emodinanthrone in Escherichia coli. Antimicrob Agents Chemotber 1986; 30(1): 147-151
[138] Andersen DO, Weber ND, Wood SG, et al. In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives. Antiviral Res 1991; 16(2):185-196
[139] Koyama M, Kelly TR, Watanabe KA. Novel type of potential anticancer agents derived from chrysophanol and emodin. J Med Chem 1988; 31:283-284
[140] Chen YC, Shen SC, Lee WR, et al. Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochem Pharmacol 2002; 64(12): 1713-1724
[141] 黄兆胜，王宗伟。大黄素基原及药理作用研究。国外医学中医中药分册 1997；19(5)：9-12
[142] 尹春琳 徐成斌 芦荟大黄素对动脉损伤后血管平滑肌细胞增殖的影响 中国中西医结合杂志 1998：18(7)：420-422
[143] 潘浩 刘学波 张红旗等 大黄素对人血管平滑肌细胞增殖的影响 解剖学研究 2004；26(2)：121-123
[144] 潘浩 葛均波 王克强 大黄素对人血管平滑肌细胞周期蛋白D1表达的影响 中国介入心脏病学杂志．2005；13(1)：37-40
[145] 何梅，夏之宁，阴永光，刘峥，紫外光谱研究中药大黄有效成分与牛血清白蛋白的相互作用 中国现代应用药学杂志 2004；21(6)：429-432
[146] Vivek Rajagopal, Stanley G Rockson. Coronary restenosis: A review of mechanisms and management. Am J Med 2003; 115:547-553
[147] Ciro Indolfi, Annalisa Mongiardo, Antonio Curcio, et al. Molecular mechanisms of in-stent restenosis and approach to therapy with eluting stents. Trends Cardiovasc Med 2003; 13: 142-148
[148] 潘长江 王进 黄楠 血管支架内再狭窄的研究进展 中国生物医学工程学杂志 2004 23(2)：152-156
[149] 潘长江，唐家驹，王进，黄楠，支架内再狭窄机理研究进展，中国介入影像与治疗学 2005；2(4)：314-317
[150] Hanke H, Strohschneider T. Time course of smooth muscle cell proliferation in the intima and media of arteries following experimental angioplasty. Circulation Research 1990; 67(3): 651-659
[151] 欧阳平，刘伊丽，许顶立等，应用PTCA导管制作大鼠颈总动脉新生
内膜增殖模型。第一军医大学学报 1999: 19 (4): 306-307
[152] S.O. Marx, T. Jayaraman, L.O. Go, A.R. Marks, Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells, Circulation Research 1995; 76: 412-417
[153] M. Poon, S.O. Marx, R. Gallo, J.J. Badimon, M.B. Taubman,A.R. Marks, Rapamycin inhibits vascular smooth muscle cell migration, J. Clin. Invest 1996; 98: 2277-2283
[154] R. Gallo, A. Padurean, T. Jayaraman, S. Marx, M. Roque, S. Adelman, J. Chesebro, J. Fallon, V. Fuster, A. Marks, J.J. Badimon, Inhibition of thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle, Circulation 1999; 99: 2164- 2170
[155] Francis J. Dumont, Qingxiang Su. Mechanism of action of the immunosuppressant rapamycin. Life Science 1996; 58(5): 373-395
[156] Arbiser JL, Klauber N, Rohan R, van Leeuwen R, Huang MT,Fisher C, Flynn E, Byers HR. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med 1998;4(6):376-83
[157] M. Hasmeda, G. M. Polya. Inhibition of cyclic AMP-dependent protein kinase by curcumin. Phytochemistry 1996; 42(3): 599-605
[158] M. F. Maitz, R. W. Y. Poon, X. Y. Liu, et al. Bioactivity of titanium following sodium plasma immersion ion implantation and deposition. Biomaterials 2005; 26: 5465-5473
[159] Axel DI, Kunert W, Goggelmann C et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation 1997; 96: 636-645
[160] Sousa JE, Costa MA, Abizaid A, et al. Two year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation 2003; 107: 381-383
[161] Martin Butzal, Sonja Loges, Michaela Schweizer, et al. Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro. Experimental cell research 2004; 300: 65-71
[162] Eugenio Stabile, Edouard Cheneau, Timothy Kinnaird, et al. Late thrombosis in cipher stents after the discontinuation of antiplatelet therapy. Cardiovascular Radiation Medicine 2004; 5:173-176
[163] 麦镇江 姜黄素的药理作用研究进展 中药材 2004；27(9)：698-701
[164] Chen HW, Huang HC. Effect of curcumin on cell cycle progression and apoptosis in vascular smooth muscle cells. Br J Pharmacol 1998; 124(6): 1029-1040
[165] Joe B, Lokesh BR. Effect of curcumin and capsaicin on arachidonic acid metabolism and lysosomal enzyme secretion by rat peritoneal macrophages. Lipids 1997;32(11):1173-1180
[166] Joe B, Lokesh BR. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochim Biophys Acta 1994; 1224(2): 255-263
[167] Abe Y, Hashimoto S, Horie T. Curcumin inhibition of in. ammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 1999; 39(1):41-7
[168] Kytai T. Nguyen, Nishat Shaikh, Kajal P. Shukla, Shih-Homg Su, Robert C. Eberhart, Liping Tang Molecular responses of vascular smooth muscle cells and phagocytes to curcumin-eluting bioresorbable stent materials. Biomaterials 2004; 25:5333-5346
[169] Dong-Hoon Hahm, Jeong-Min Kim, Jonghoe Byun, et al. Development of a novel drug-coated stent using curcumin as antiproliferative drug. Poster Abstracts / Cardiovascular Pathology 2004; 13: S135
[170] 洪行球 赵革平 黄燕芬 刘艳 姜黄醇提取物中不同组分对血管平滑肌细胞增殖的影响研究 中医药学刊 2004：22(10)：1823-1825
[171] Waylon M. Weber, Lucy A. Hunsaker, Steve F. Abcouwer, Lorraine M. Deck and David L. Vander Jagt. Anti-oxidant activities of curcumin and related enones. Bioorganic & Medicinal Chemistry 2005; 13: 3811-3820
[172] Sousa JE, Costa MA, Sousa AG, et al. Two-year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation 2003; 107(3): 381-383
[173] Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346(23): 1773-1780
[174] Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349(14): 1315-1323
[175] McMahon LP, Choi KM, Lin TA, et al. The rapamycin binding domain governs substrate selectivity by mammalian target of rapamycin. Mol Cell Biol 2002; 22(21): 7428-7438
[176] Dennis PB, Fumagalli S, Thomas G Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and degration. Curr OpinGenet Dev 1999; 9(1): 49-54
[177] Chiu MI, Katz H, Berlin V. APT1, a mammalian homologue of yeast TOR interacts with the FKBP12-Rapamycin complex. Proc Natl Acad Sci USA 1994: 91(26): 12574-12578
[178] Sehgal SN. Rapamune (Sirolimus, Rapamycin): An overview and mechanism of action. Ther Frug Monit 1995; 17(6): 660-665
[179] Beretta L, Gingras AC, Svitkin YV et al. Rapamycin blocks the phosphorylation of 4EBP1 and inhibits cap-dependent iniation of translation. EMBO J 1996; 15(3): 658-664
[180] Von Manteuffel Sr, Dennis PB, Ullen N, et al. The insulin induced signaling pathway leading to S6 and initiation factor 4E binding protein phosphorylation bifurcates at a rapamycin sensitive point immediately upstream of P70S6K. Mol Cell Biol 1997; 17(9): 5426-5436
[181] Hashermolhosseini S, Nagamine Y, Morley SJ. Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem 1998; 273(23): 14424-14429
[182] Kjeld Christensen,Rolf Larsson,Hakan Emanuelsson etc. Heparin coating of the stent graft-effects on platelets,coagulation and complement activation. Biomaterials 2001; 22: 349-355
[183] Matty CM. Vrolix, Victor M. Legrand, Johan H.C. Reiber, et al. Heparin-coated wiktor stents in human coronary arteries. The American Journal of Cardiology 2000; 86: 385-389
[184] Alt E, Haehnel I, Beilharz C, et al. Inhibition of neointima formation after experimental coronary artery stenting: a new biodegradable stent coating releasing hirudin and proctacyclin analogue iloprost. Circulation 2000; 101: 1453-1458
[2] 奚廷斐. 生物材料进展(二). 生物医学工程与临床 2004; 8(4): 244-248
[3] E Regar, G Sianos, P W Serruys. Stent development and local drug delivery. British Medical Bulletin 2001 ;59: 227-248
[4] Teirstein P.S, Massullo V, Jani S, et al. Three-year clinical and angiographic follow-up after intracoronary radiation: Results of a randomized clinical trial. Circulation 2000; 101:360-365
[5] Monnink SH, van Boven AJ, Peels HO, et al. Silicon-carbide coated coronary stents have low platelet and leukocyte adhesion during platelet activation. J Investig Med 1999; 47:304-310
[6] K. Gutensohn, C. Beythien, J. Bau, et al. In vitro analyses of diamond-like carbon coated stents: Reduction of metal ion release, platelet activation, and thrombogenicity. Thrombosis Research 2000; 99: 577-585
[7] Aude M, Erbel R, Issa H, Meyer J. Quantitative analysis of elastic recoil after balloon angioplasty and after intracoronary implantation of balloon-expandable Palmaz-Schatz stents. Am J Cardiol 1987; 60: 20B-28B
[8] Lowe HC, Oesterle SN, Khachigian LM. Coronary in-stent restenosis: current status and future strategies. J Am Coll Cardiol 2002; 39(2): 183-193
[9] Hoffmann R, Mintz GS, Dussaillant GR, et al. Patterns and mechanism of in-stent restenosis. A serial intravascular ultrasound study. Circulation 1996; 94(6): 1247-1254
[10] Grewe P.H, Deneke T, Machraoui A. et al. Acute and chronic tissue response to coronary stent implantation: pathologic findings in human specimen. J Am Coll Cardiol 2000; 35: 157-163
[11] Robert S. Schwartz. Pathophysiology of restenosis: interaction of thrombosis, hyperplasia and/or remodeling. The American Journal of Cardiology 1998; 81(7A): 14E-17E
[12] Rekhter M.D, O'Brien E, Shah N et al. The importance of thrombus organization and stellate cell phenotype in collagen I gene expression in human, coronary atherosclerotic and restenotic lesions. Cardiovasc Res 1996; 32: 496-502
[13] 赵革平，沃兴德，洪行德，刘德文．姜黄醇提取物对血管平滑肌细胞增殖的影响．浙江中医学院学报 1997：23(3)：21-23
[14] Bauters C, de Groote P, Adamantidis M, et al. Proto-oncogene expression in rabbit aorta after wall injury. First marker of the cellular process leading to restenosis after angioplasty?. Eur Heart J 1992; 13:556-559
[15] Moreno P. R, Palacios I. F, Leon M. N. et al. Histopathologic comparison of human coronary in-stent and post-balloon angioplasty restenotic tissue. Am J Cardiol 1999; 84:462-466
[16] Farb A, Sangiorgi G, Carter A. J. et al. Pathology of acute and chronic coronary stenting in humans. Circulation 1999; 99:44-52
[17] Baurschmidt P, Schaldach M. Electrochemical aspects of the thrombogenicity of a materials. Journal of Bioengineering 1997; 1(11): 261-267
[18] Bartorelli AL, Trabattoni D, Montorsi P, et al. Aspirin alone antiplatelet regimen after intracoronary placement of Carbostent: the ANTARES study. Catheter Cardiovasc Interv 2002; 55:150-156
[19] Antoniucci D, Bartorelli A, Vaenti R, et al. Clinical and angiographic outcome after coronary artery stenting with the Carbostent. Am J Cardiol 2000; 85: 821-825.
[20] Antoniucci D, Vaenti R, Migliorini A, et al. Clinical and angiographic outcomes following elective implantation of Carbostent in patients at high risk of restenosis and target vessel failure. Cathet Cardiovasc Interv 2001; 54:420-426
[21] Van der Giessen W, van Beusekom HM, Hofma SH et al. Preliminary results with bi-component metal-biodegradable polymer stents in porcine coronary mode. Eur Heart J 1996;17:178
[22] Lewis AL. Phosphorylcholine-based polymers and their use in the prevention of biofouling. Coll Surf B 2000; 18:261-275
[23] AL Lewis, LA Tolhurst, PW Stratford. Analysis of a phosphorylcholine-based polymer coating on a coronary stent pre- and post-implantation. Biomaterials 2002; 23:1697-1706
[24] AL Lewis, Zoie L, Cumming Hind, H. Goreish et al. Crosslinkable coatings from phosphorylcholine-based polymers. Biomaterials 2001;22:99-111
[25] Toutouzas K, Stefanadis C, Tsiamis E et al. Effects of stents coated by an autologous vein graft on intima hyperplasia in porcine coronary arteries. J Am Coll Cardiol 1998;31:414-421
[26] Toutouzas K, Stefanadis C, Tsiamis E et al. Autologous vein-graft covered steut for the treatment of coronary artery disease:immediate and long-term results. Eur Heart J 1998;19:498-505
[27] 潘长江，王进，黄楠．血管支架内再狭窄的研究进展．中国生物医学工程学学报 2004；23(2)：152-156
[28] Elezi S, Kastrati A, Neumann F. J. et al. Vessel size and long-term outcome after coronary stent placement. Circulation 1998; 98:1875-1880
[29] Sousa JE, Serruys PW, Costa MA. New frontiers in cardiology: drug-eluting stents: Part 1. Circulation 2003; 107:2274-2279
[30] Samer M. Garas, Philip Huber, Neal A. Scott. Overview of therapies for prevention of restenosis after coronary interventions. Pharmacology & Therapeutics 2001; 92:165-178
[31] Kjeld Christensen, Roll Larsson, Hakan Emanuelsson et al. Heparin coating of the stent graft-effects on platelets, coagulation and complement activation. Biomaterials 2001; 22:349-355
[32] Young Keun Ahn, MD, Myung Ho Jeong et al. Preventive effects of the heparin-coated steut on restenosis in the porcine model. Catheterization and Cardiovascular Interventions 1999; 48:324-331
[33] Francis J. Dumont, Qingxiang Su. Mechanism of action of the immunosuppressant rapamycin. Life science 1996; 58(5): 373-395
[34] Klugherz BD, Llanos G, Lieuallen W, et al. Tweuty-eight-day efficacy and pharmacokinetics of the sirolimus-eluting stent. Coron Artery Dis 2002; 13: 183-188
[35] Anand Babu Dhanikula, Ramesh Panchagnula. Localized paclitaxel delivery. International Journal of Pharmaceutica 1999; 183: 85-100
[36] Axel DI, Kunert W, Goggelmann C et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation 1997; 96:636-645
[37] Rowinsky EK, Donehower RC. Paclitaxel(taxol). N Eng J Med 1995; 332(15):1004-1014
[38] K. T. Nguyen, S. -H. Su, A. Sheng, et al. In vitro hemocompatibility studies of drug-loaded poly-(l-lactic acid) fibers. Biomaterials 2003; 24:5191-5201
[39] Kytai T. Nguyen, Nishat Shaikh, Kajal P. Shukla, et al. Molecular responses of vascular smooth muscle cells and phagocytes to curcumin-eluting bioresorbable stent materials. Biomaterials 2004; 25:5333-5346
[40] 尹春琳，徐成斌．大黄素对血管平滑肌细胞增生抑制作用的机制．北京医科大学学报 1998；30(6)：515-517
[41] Barone GW, Conerly JM, Farley PC. et al. Endothelial injury and vascular dysfunction associated with the Fogarty balloon catheter. J Vasc Surg 1989; 9(3): 422-425
[42] Laitinen M, Hartikainen J, Hiltunen MO, et al. Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. Human Gene Ther 2000; 11(2): 263-270
[43] Neil Swanson, Kai Hogrefe, Qamar Javed, Anthony H. Gershlick. In vitro evaluation of vascular endothelial growth factor (VEGF)-eluting stents. International Journal of Cardiology 2003; 92:265-269
[44] Van der Giesen WJ, Lincoff AM, Schwartz RS, etc. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation 1996; 94(7): 1690-1697
[45] Barend L. Van der Hoeven, Nuno M.M. Piers, Hazem M. Warda, et al. Drug-eluting stents: results, promises and problems. International Journal of Cardiology 2005; 99:9-17
[46] Palmaz JC, Bailey S, Marton D, Sprague E. Influence of stent design and material composition on procedure outcome. J Vasc Surg 2002; 36(5): 1031-1039
[47] Virmani R, Kolodgie FD, Farb A, et al. Drug-eluting stents: are human and animal studies comparable?. Heart 2003; 89(2): 133-138
[48] Long-term effects of stem-based delivery of sirolimus in the porcine model. Am J Cardiol 2002; 90(6A): TCT199
[49] Welt FGP, Rogers C. Inlammation and restenosis in the stent era. Arterioscl Thromb Vasc Biol 2002;22:1769-1776.
[50] Sousa JE, Costa MA, Abizaid A, et al. Two year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation 2003; 107:381-383
[51] Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346(23): 1773-1780
[52] Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents verus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003; 349(14): 1315-1323
[53] Schofer J, Schluter M, Gershlick AH, et al. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomized controlled trial (E-SIRIUS). Lancet 2003; 362(9390): 1093-1099
[54] Curcio A, Torella D, Guda G, et al. Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis. Am J Physiol Heart Circ Physiol 2004; (286): 902-908
[55] Babinska A, Markell MS, Salifu MO, et al. Enhancement of human platelet aggregation and secretion induced by rapamycin. Nephrol Dial Transplant 1998; 13(12): 3153-3159
[56] 周保国，李红梅．黄连素在心血管疾病中的应用研究进展．实用中西医结合杂志 1997；10(7)：609-609
[57] Neil Swanson, Kai Hogrefe, Qamar Javed, et al. In vitro evalution of vascular endothelial growth factor (VEGF)-eluting stents. International Journal of Cardiology 2003; 92:265-269
[58] Barend L. van der Hoeven, Nuno M. M. Pires, Hazem M. Warda, et al. Drug-eluting stents: results, promises and problems. International Journal of Cardiology 2005; 99:9-17
[59] Alt E, Haehnel I, Beilharz C, Prietzel K, et al. Inhibition of neointima formation after experimental coronary artery stenting: a new biodegradable stent coating releasing hirudin and proctacyclin analogue iloprost. Circulation 2000; 101:1453-1458
[60] Samer M. Garas, Philip Huber, Neal A. Scott. Overview of therapies for prevention of restenosis after coronary interventions. Pharmacology & Therapeutics 2001; 92:165-178
[61] Vivek Rajagopal, Stanley G. Rockson. Coronary restenosis: A review of mechanisms and management. The American Journal of Medicine 2003; 115: 547-553
[62] Martin R. Bennett, Michael O'Sullivan. Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy. Phamacology & Therapeutics 2001; 91: 149-166.
[63] Mei-Chin Chen, Hsiang-Fa Liang, Ya-Ling Chiu, et al. A novel drug-eluting stent spray-coated with multi-layers of collagen and sirolimm. Journal of controlled release 2005; 108:178-189
[64] 平其能等编著 现代药剂学 中国医药科技出版社 北京 2001．7第一版
[65] J. Eduardo Soma, Patrick W. Serruys, Marco A. Costa. New frontiers in cardiology: Drug-eluting stems: Part Ⅰ. Circulation 2003; 107:2274-2279
[66] 陈建海主编 药用高分子材料与现代药剂 科学出版社 北京 2003．8第一版
[67] Lens, PFH Harmsen etc. Immobilization of functionalized alkyl-poly(ethylene oxide) surfactants on poly(ethylene) surfaces by means of an argon plasma treatment. J Biomater Sci. Polymer Edn 1997; 18(12): 963-971
[68] Mansoor Amiji, Kinam Park. Surface modification of polymeric biomatedals with poly(ethylene oxide),albumin and heparin for reduced thrombogenieity. J Biomater Sci. Polymer Edn 1993; 4(3): 217-227
[69] Merill EW, Salzman EW. Poly(ethylene oxide) as a biomaterials. Am Soc Artif Intern Organ 1983; 6:60-72
[70] Ron Waksman. Drug-eluting stents: From bench to bed. Cardiovascular Radiation Medicine 2002; 3:226-241
[71] E Regar, G Sianos and P W Serruys. Stent development and local drug delivery. British Medical Bulletin 2001 ;59: 227-248
[72] Shrirang V. Ranade, Kathleen M. Miller, Robert E. Richard, et al. Physical characterization of controlled release of paclitaxel from the TAXUSTM Express2TM drug-eluting stent. J Biomed Mater Res 2004; 71 A: 625-634
[73] Finkelstein A, McClean D, Kar S, et al. Local drug delivery via a coronary stent with programmable release pharmacokinetics. Circulation 2003; 107(5): 777-784
[74] Curcio A, Torella D, Cuda G, et al. Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis. Am J Physiol Heart Circ Physiol 2004; (286):902-908
[75] Virmani R, Kolodgie FD, Farb A, Lafont A. Drug eluting stents: are human and animal studies comparable?. Heart 2003;89(2): 133-138.
[76] Babinska A, Markell MS, Salifu MO, et al. Enhancement of human platelet aggregation and secretion induced by rapamycin. Nephrol Dial Transplant 1998; 13(12): 3153-3159
[77] Willem J. van der Giessen, Heleen M.M. van Beusekom, Rolf Larsson, Patrick W. Serruys. Heparin-coated coronary stents. Current Interventional Cardiology Reports 1999;1: 234-240;
[78] Eli I. Lev, Abid R. Assali, Lgal Teplisky, et al. Comparison of outcomes up to six months of heparin-coated with noncoated stents after percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2004; 93: 741-743
[79] Huang, M. T., Lysz, T., Ferraro, T., Abidi, T. F., Laskin, J. D., & Conney, A. H.. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Research 1991; 51: 813-819
[80] Panchatcharam Manikandan, Miriyala Sumitra , Srinivasan Aishwarya, Bhakthavatsalam Murali Manohar, Beema Lokanadamc, Rengarajulu Puvanakrishnan. Curcumin modulates free radical quenching in myocardial ischaemia in rats. The International Journal of Biochemistry & Cell Biology 2004; 36: 1977-1990;
[81] Kytai T. Nguyen, Nishat Shaikh, Kajal P. Shukla, Shih-Horng Su, Robert C. Eberhart, Liping Tang Molecular responses of vascular smooth muscle cells and phagocytes to curcumin-eluting bioresorbable stent materials. Biomaterials 2004; 25: 5333-5346
[82] Mohan N. Babapulle, Mark J. Eisenberg. Coated stents for the prevention of restenosis: Part II. Circulation 2002; 106: 2859-2866
[83] Samer M. Garas, Philip Huber, Neal A. Scott. Overview of therapies for prevention of restenosis after coronary interventions. Pharmacology & Therapeutics 2001; 92: 165-178
[84] I.De Scheerder, J. Sohier, E. Verbeken, et al. Biocompatibility of coronary stent materials: Effect of electrochemical polishing. Electropolishing 2001; 32: 142-148
[85] De Scheerder I, Verbeken E, Van Humbeeck. Metallic surface modification. Semin Interv Cardiol 1998; 3: 139-144
[86] Tepe G, Wendel HP, Khorchidi S et al. Thrombogenicity of various endovascular stent types: an in vitro evaluation. J vasc Interv Radiol 2002; 13:1029-1035
[87] Palmz JC, Benson A, Sprague EA. Influence of surface topography on endothelialization of intravascular metallic material. J Vasc Interv Radiol 1999; 10:439-444
[88] Van Belle E, Tio FO, Couffinhal T, Maillard L, Passed J, Isner JM. Stent endothelialization. Time course, impact of local catheter delivery, feasibility of recombinant protein administration, and response to cytokine expedition. Circulation 1997;95:438-448
[89] P.W. Heyman, C.S. Cho, J.C. Mcrea, et al. Heparinized polyurethanes: in vitro and in vivo studies. J Biomed Mater Res 1985; 19: 419-436
[90] W.LJ. Himrichs, H.W.M. Ten Hoopen, M.J.B. Wissink, et al. Design of a new type of coating for the controlled release of heparin. Journal of controlled release 1997; 45: 163-176
[91] Camiel C.L Peerlings, Hans H.L.Hanssen, Raymond T.J.Bevers, et al. Heparin release from Slippery-when-wet guides wires for intravascular use. J Biomed Mater Res (Appl Biomater) 2002; 63:692-698
[92] Kjeld Christensen, Rolf Larsson, Hakan Emanuelsson, et al. Improved blood compatibility of a stent graft by combining heparin coating and abciximab. Thrombus Research 2005; 115:245-253
[93] Mingchao shen, etc. PEO-like plasma polymerized tetraglyme surface interactions with leukocytes and proteins: in vitro and in vivo studies. J Biomater Sci. Polymer. Edn. 2002; 13(4):367-375
[94] 许海燕 孔桦 杨子彬 抗凝血高分子材料的研究进展及其在心血管外科中的应用 高分子材料科学与工程 2001；17(5)：167-169
[95] Harry C. Lowe, Stephen N. Oesterle, Levon M. Khachigian. Coronary in-stent restenosis: Current status and future strategies. Journal of the American College of Cardiology 2002; 39(2): 183-193
[96] Bennett MR, O'Sullivan M. Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy. Pharmacol Ther 2001; 91:149-166
[97] Farb A, Sangiorgi G, Carter AJ, et al. Pathology of acute and chronic coronary stenting in humans. Circulation 1999; 99:44-52
[98] Kastrati A, Mehilli J, Dirschinger J, et al. Restenosis after coronary placement of various stent types. Am J Cardiol 2001; 87:34-39
[99] Finkelstein A, McClean D, Kar S, et al. Local drug delivery via a coronary stent with programmable release pharmacokinetics. Circulation 2003; 107:777-784.
[100] Sousa JE, Sousa AG, Costa MA, Abizaid AC, Feres F. Use of rapamycin impregnated stents in coronary arteries. Transplant Proc 2003; 35:S165-S170.
[101] Oberhoff M, Herdeg C, Baumbaeh A, Karsch KR. Stent-based antirestenotic coatings (sirolimus/paclitaxel). Cathet Cardiovasc Interv 2002; 55:404-408
[102] Frank Alexis, Subbu S. Venkatraman, Santosh Kumar Rath, Freddy Boey. In vitro study of release mechanisms of paelitaxel and rapamyein from drug-incorporated biodegradable stent matrices. Journal of controlled release 2004; 98:67-74
[103] 李又欣 冯新德 控制药物释放体系及其机理 高分子学报 1991；19(1)： 19-27
[104] 杨亚楠 尹静波 刘芳 高分子材料在药物控制释放方面的应用 吉林工学院学报 2001：22(3)：38-40
[105] C. W. Hwang, D. Wu, E. R. Edelman. Impact of transport and drug properties on the local pharmacology of drug-eluting stents. International Journal of Cardiovascular Interventions 2003; 5: 7-12
[106] E. C. SIMS, M. T. ROTHMAN, T. D. WARNER, M. E. B. POWELL. Coronary Artery Brachytherapy. Clinical Oncology (2002) 14:313-326
[107] Gordon A. A. Ferns, Tony Y. Avades. The mechanism of coronary restenosis: insights from experimental models. International Journal of Experimental Pathology 2000; 81:63-88
[108] P. B. J. Burton, M. H. Yacoub, P. J. R. Barton, Rapamycin (Sirolimus) inhibits heart cell growth in vitro, Pediatr. Cardiol 1998; 19: 468-470
[109] 尹春琳，徐成斌．芦荟大黄素对动脉损伤后血管平滑肌细胞增殖的影响 中国中西医结合杂志 1998：18(7)：420-422
[110] Dong-Hoon Hahm, Jeong-Min Kim, Jonghoe Byun, et al. Development of a novel drug-coated stent using eurcumin as antiproliferative drug. Poster Abstracts, Cardiovascular Pathology 2004; (13):S80-S138
[111] Ron Waksman. Drug-eluting stents: From bench to bed. Cardiovascular Radiation Medicine 2002; 3:226-241
[112] Shrirang V. Ranade, Kathleen M. Miller, Robert E. Richard, et al. Physical characterization of controlled release of paclitaxel from the TAXUSTM Express2TM drug-eluting stent. J Biomed Mater Res 2004; 71A: 625-634
[113] Felix C. Tanner, Zhi-Yong Yang, Eric Duckers, et al. Expression of Cyclin-dependent kinase inhibitors in vascular disease. Circulation Research 1998; 82:396-403
[114] J. Eduardo Sousa, Patrick W. Serruys, Marco A. Coata. New frontiers in cardiology: drug-eluting stents Part Ⅰ. Circulation 2003; 107:2274-2279
[115] M. Poon, S. O. Marx, R. Gallo, J. J. Badimon, M. B. Taubman, A. R. Marks, Rapamycin inhibits vascular smooth muscle cell migration, J. Clin. Invest 1996; 98:2277-2283
[116] Frank Alexis, Subbu S. Venkatraman, Santosh Kumar Rath, Freddy Boey. In vitro study of release mechanisms of paclitaxel and rapamycin from drug-incorporated biodegradable stent matrices. Journal of Controlled Release 2004; 98: 67-74
[117] Maud B. Gorbet, Michael V. Sefton. Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. Biomaterials 2004; 25:5681-5703
[118] Diran Basmadjian, Michael V, Sefton etc. Coagulation on biomaterials in flowing blood: some theoretical consideration. Biomaterials 1997; 18:1511-1520
[119] 许海燕 孔桦 杨子彬 抗凝血高分子材料的研究进展及其在心血管外科中的应用 高分子材料科学与工程 2001；17(5)：167-171
[120] Alexander Welle, Michael Grunze, Dsidra Tur. Plasma protein adsorption and platelet adhesion on poly[bis(trifluoroethoxy)phosphazene] and reference materials surfaces. Journal of colloid and interface science 1998; 197:263-274
[121] R. J. Green, M. C. Davies, C. J. Roberts, et al. Competitive protein adsorption as observed by surface plasmon resonance. Biomaterials 1999; 20: 385-391
[122] 胡国栋．聚氨酯的血液相容性评价．国外医学生物医学工程分册，2002；25(6)：271-273
[123] 王传华，冷希岗．生物材料诱发血栓形成机制的研究进展．国外医学生物医学工程分册，1998：21(1)：1-5
[124] 王春仁．生物材料表面血浆蛋白的吸附．国外医学生物医学工程分册，1995：18(6)：334-337
[125] 奚廷斐，王春仁，田文华，雷学会．生物材料血液相容性综合评价体系的研究．中国生物医学工程学报，1989：8(4)：212-221
[126] 石晶 吴树荣 姜黄素对大鼠血小板聚集和血栓形成的影响 军医进修学院学报 1996：17(1)：31-33
[127] 沃兴德，崔小强，唐利华．姜黄素对食饵性高脂血症大鼠血浆脂蛋白代谢相关酶活性的影响．中国动脉硬化杂志，2003，11(3)：223-226
[128] Srivastava R, Puri V, Srimal RC, et al. Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. Arzneimittelfors- chung, 1986;36(4): 715-717
[129] Shah BH, Nawaz Z, Pertani SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acidmediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol, 1999;58(7): 1167-1172
[130] Huang, M. T, Lysz, T, Ferraro, T, Abidi, et al. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Research 1991: 51: 813-819
[131] K. T. Nguyen, S. -H. Su, A. Sheng, D. Wawro, et al. In vitro hemocompatibility studies of drug-loaded poly-(l-lactic acid) fibers. Biomaterials 2003; 24:5191-5201
[132] Panchatcharam Manikandan, Midyala Sumitra, Srinivasan Aishwarya, Bhakthavatsalam Murali Manohar, Beema Lokanadamc, Rengarajulu Puvanakrishnan. Curcumin modulates free radical quenching in myocardial ischaemia in rats. The International Journal of Biochemistry & Cell Biology 2004; 36:1977-1990
[133] Babinska A, Markell MS, Salifu MO, et al. Enhancement of human platelet aggregation and secretion induced by rapamycin. Nephrol Dial Transplant 1998; 13(12): 3153-3159
[134] 万征，蔡衡，李晓春等．雷帕霉素药物洗脱支架的临床应用研究．天津医学 2004；32(9)：511-513，，
[135] Yvette B. J. Aldenhoff, Menno L. W. Knetsch, Johannes H. L. Hanssen, Theo Lindhout, et al. Coils and tubes releasing hepadn. Studies on a new vascular graft prototype. Biomaterials 2004; 25:3125-3133
[136] Kjeld Christensen, Rolf Larsson, Hakan Emanuelsson, et al. Improved blood compatibility of a stent graft by combining heparin coating and abciximab. Thrombus Research 2005; 115:245-253
[137] Ubbink-kok T, Anderson JA, Konings WN. Inhibition of electron transfer and uncoupling effects by emodin and emodinanthrone in Escherichia coli. Antimicrob Agents Chemotber 1986; 30(1): 147-151
[138] Andersen DO, Weber ND, Wood SG, et al. In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives. Antiviral Res 1991; 16(2):185-196
[139] Koyama M, Kelly TR, Watanabe KA. Novel type of potential anticancer agents derived from chrysophanol and emodin. J Med Chem 1988; 31:283-284
[140] Chen YC, Shen SC, Lee WR, et al. Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochem Pharmacol 2002; 64(12): 1713-1724
[141] 黄兆胜，王宗伟。大黄素基原及药理作用研究。国外医学中医中药分册 1997；19(5)：9-12
[142] 尹春琳 徐成斌 芦荟大黄素对动脉损伤后血管平滑肌细胞增殖的影响 中国中西医结合杂志 1998：18(7)：420-422
[143] 潘浩 刘学波 张红旗等 大黄素对人血管平滑肌细胞增殖的影响 解剖学研究 2004；26(2)：121-123
[144] 潘浩 葛均波 王克强 大黄素对人血管平滑肌细胞周期蛋白D1表达的影响 中国介入心脏病学杂志．2005；13(1)：37-40
[145] 何梅，夏之宁，阴永光，刘峥，紫外光谱研究中药大黄有效成分与牛血清白蛋白的相互作用 中国现代应用药学杂志 2004；21(6)：429-432
[146] Vivek Rajagopal, Stanley G Rockson. Coronary restenosis: A review of mechanisms and management. Am J Med 2003; 115:547-553
[147] Ciro Indolfi, Annalisa Mongiardo, Antonio Curcio, et al. Molecular mechanisms of in-stent restenosis and approach to therapy with eluting stents. Trends Cardiovasc Med 2003; 13: 142-148
[148] 潘长江 王进 黄楠 血管支架内再狭窄的研究进展 中国生物医学工程学杂志 2004 23(2)：152-156
[149] 潘长江，唐家驹，王进，黄楠，支架内再狭窄机理研究进展，中国介入影像与治疗学 2005；2(4)：314-317
[150] Hanke H, Strohschneider T. Time course of smooth muscle cell proliferation in the intima and media of arteries following experimental angioplasty. Circulation Research 1990; 67(3): 651-659
[151] 欧阳平，刘伊丽，许顶立等，应用PTCA导管制作大鼠颈总动脉新生
内膜增殖模型。第一军医大学学报 1999: 19 (4): 306-307
[152] S.O. Marx, T. Jayaraman, L.O. Go, A.R. Marks, Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells, Circulation Research 1995; 76: 412-417
[153] M. Poon, S.O. Marx, R. Gallo, J.J. Badimon, M.B. Taubman,A.R. Marks, Rapamycin inhibits vascular smooth muscle cell migration, J. Clin. Invest 1996; 98: 2277-2283
[154] R. Gallo, A. Padurean, T. Jayaraman, S. Marx, M. Roque, S. Adelman, J. Chesebro, J. Fallon, V. Fuster, A. Marks, J.J. Badimon, Inhibition of thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle, Circulation 1999; 99: 2164- 2170
[155] Francis J. Dumont, Qingxiang Su. Mechanism of action of the immunosuppressant rapamycin. Life Science 1996; 58(5): 373-395
[156] Arbiser JL, Klauber N, Rohan R, van Leeuwen R, Huang MT,Fisher C, Flynn E, Byers HR. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med 1998;4(6):376-83
[157] M. Hasmeda, G. M. Polya. Inhibition of cyclic AMP-dependent protein kinase by curcumin. Phytochemistry 1996; 42(3): 599-605
[158] M. F. Maitz, R. W. Y. Poon, X. Y. Liu, et al. Bioactivity of titanium following sodium plasma immersion ion implantation and deposition. Biomaterials 2005; 26: 5465-5473
[159] Axel DI, Kunert W, Goggelmann C et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation 1997; 96: 636-645
[160] Sousa JE, Costa MA, Abizaid A, et al. Two year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation 2003; 107: 381-383
[161] Martin Butzal, Sonja Loges, Michaela Schweizer, et al. Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro. Experimental cell research 2004; 300: 65-71
[162] Eugenio Stabile, Edouard Cheneau, Timothy Kinnaird, et al. Late thrombosis in cipher stents after the discontinuation of antiplatelet therapy. Cardiovascular Radiation Medicine 2004; 5:173-176
[163] 麦镇江 姜黄素的药理作用研究进展 中药材 2004；27(9)：698-701
[164] Chen HW, Huang HC. Effect of curcumin on cell cycle progression and apoptosis in vascular smooth muscle cells. Br J Pharmacol 1998; 124(6): 1029-1040
[165] Joe B, Lokesh BR. Effect of curcumin and capsaicin on arachidonic acid metabolism and lysosomal enzyme secretion by rat peritoneal macrophages. Lipids 1997;32(11):1173-1180
[166] Joe B, Lokesh BR. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochim Biophys Acta 1994; 1224(2): 255-263
[167] Abe Y, Hashimoto S, Horie T. Curcumin inhibition of in. ammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 1999; 39(1):41-7
[168] Kytai T. Nguyen, Nishat Shaikh, Kajal P. Shukla, Shih-Homg Su, Robert C. Eberhart, Liping Tang Molecular responses of vascular smooth muscle cells and phagocytes to curcumin-eluting bioresorbable stent materials. Biomaterials 2004; 25:5333-5346
[169] Dong-Hoon Hahm, Jeong-Min Kim, Jonghoe Byun, et al. Development of a novel drug-coated stent using curcumin as antiproliferative drug. Poster Abstracts / Cardiovascular Pathology 2004; 13: S135
[170] 洪行球 赵革平 黄燕芬 刘艳 姜黄醇提取物中不同组分对血管平滑肌细胞增殖的影响研究 中医药学刊 2004：22(10)：1823-1825
[171] Waylon M. Weber, Lucy A. Hunsaker, Steve F. Abcouwer, Lorraine M. Deck and David L. Vander Jagt. Anti-oxidant activities of curcumin and related enones. Bioorganic & Medicinal Chemistry 2005; 13: 3811-3820
[172] Sousa JE, Costa MA, Sousa AG, et al. Two-year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation 2003; 107(3): 381-383
[173] Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346(23): 1773-1780
[174] Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349(14): 1315-1323
[175] McMahon LP, Choi KM, Lin TA, et al. The rapamycin binding domain governs substrate selectivity by mammalian target of rapamycin. Mol Cell Biol 2002; 22(21): 7428-7438
[176] Dennis PB, Fumagalli S, Thomas G Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and degration. Curr OpinGenet Dev 1999; 9(1): 49-54
[177] Chiu MI, Katz H, Berlin V. APT1, a mammalian homologue of yeast TOR interacts with the FKBP12-Rapamycin complex. Proc Natl Acad Sci USA 1994: 91(26): 12574-12578
[178] Sehgal SN. Rapamune (Sirolimus, Rapamycin): An overview and mechanism of action. Ther Frug Monit 1995; 17(6): 660-665
[179] Beretta L, Gingras AC, Svitkin YV et al. Rapamycin blocks the phosphorylation of 4EBP1 and inhibits cap-dependent iniation of translation. EMBO J 1996; 15(3): 658-664
[180] Von Manteuffel Sr, Dennis PB, Ullen N, et al. The insulin induced signaling pathway leading to S6 and initiation factor 4E binding protein phosphorylation bifurcates at a rapamycin sensitive point immediately upstream of P70S6K. Mol Cell Biol 1997; 17(9): 5426-5436
[181] Hashermolhosseini S, Nagamine Y, Morley SJ. Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem 1998; 273(23): 14424-14429
[182] Kjeld Christensen,Rolf Larsson,Hakan Emanuelsson etc. Heparin coating of the stent graft-effects on platelets,coagulation and complement activation. Biomaterials 2001; 22: 349-355
[183] Matty CM. Vrolix, Victor M. Legrand, Johan H.C. Reiber, et al. Heparin-coated wiktor stents in human coronary arteries. The American Journal of Cardiology 2000; 86: 385-389
[184] Alt E, Haehnel I, Beilharz C, et al. Inhibition of neointima formation after experimental coronary artery stenting: a new biodegradable stent coating releasing hirudin and proctacyclin analogue iloprost. Circulation 2000; 101: 1453-1458