比较雷公藤内酯醇与西罗莫司洗脱支架预防再狭窄

目的 比较雷公藤内酯醇洗脱支架与西罗莫司(sirolimus,雷帕霉素)洗脱支架预防冠状动脉支架植入术后再狭窄的作用.方法 选用杂种幼猪30只,随机分成裸支架组、雷公藤内酯醇洗脱支架组和西罗莫司洗脱支架组,每组各植入支架10枚.术后28 d,进行冠状动脉造影、组织病理检查以及免疫组化检测血管平滑肌细胞中增殖细胞核抗原(proliferating cell nuclear antigen,PCNA).结果 雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组支架内最小内径相似(P＞0.05),均大于裸支架组(P＜0.01);雷公藤内酯醇洗脱支架组新生内膜面积与西罗莫司洗脱支架组相似(P＞0.05),均小于裸支架组(P＜0.01).雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组的PCNA阳性细胞数相似(P＞0.05),均少于裸支架组(P＜0.01).结论 雷公藤内酯醇洗脱支架能抑制平滑肌细胞增殖,其预防冠状动脉支架内再狭窄的作用与西罗莫司洗脱支架相似.     

雷公藤内酯醇洗脱支架与雷帕霉素洗脱支架对冠状动脉支架内再狭窄作用的对比研究

目的 比较雷公藤内酯醇洗脱支架与西罗莫司（sirolimus,雷帕霉素）洗脱支架预防冠状动脉支架植入术后再狭窄的作用.方法 选用杂种幼猪30只,随机分成裸支架组、雷公藤内酯醇洗脱支架组和西罗莫司洗脱支架组,每组各植入支架10枚.术后28 d,进行冠状动脉造影、组织病理检查以及免疫组化检测血管平滑肌细胞中增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）.结果 雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组支架内最小内径相似（P＞0.05）,均大于裸支架组（P＜0.01）;雷公藤内酯醇洗脱支架组新生内膜面积与西罗莫司洗脱支架组相似（P＞0.05）,均小于裸支架组（P＜0.01）.雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组的PCNA阳性细胞数相似（P＞0.05）,均少于裸支架组（P＜0.01）.结论 雷公藤内酯醇洗脱支架能抑制平滑肌细胞增殖,其预防冠状动脉支架内再狭窄的作用与西罗莫司洗脱支架相似.     

Mytrolimus药物洗脱支架预防支架内再狭窄的实验研究

目的评价新型聚烯烃类高分子化合物涂层携载雷帕霉素衍生物-Mytrolimus(CCI-779)洗脱支架在小型猪冠状动脉模型预防再狭窄的疗效。方法小型猪冠状动脉分别置入裸支架、单纯聚烯烃类高分子化合物涂层支架和Mytrolimus洗脱支架(160μg/18mm)。术后4周重复冠状动脉造影后处死动物,测定3组支架血管段的损伤指数、冠状动脉横截面积、管腔面积、支架上平均内膜厚度、支架间平均内膜厚度、新生内膜面积、面积再狭窄百分比,并作比较。结果裸支架组(置入支架数n=10)、单纯聚烯烃类高分子化合物涂层支架组(n=10)和Mytrolimus洗脱支架组(n=8)3组冠状动脉大小和血管损伤程度基本相同,术后4周,单纯聚烯烃类高分子化合物涂层组与裸支架比较多项参数差异均无统计学意义。Mytrolimus药物洗脱支架组和裸支架组的支架上内膜厚度分别为(0.18±0.08)mm和(0.33±0.25)mm(P<0.05);支架间内膜厚度分别为(0.14±0.05)mm和(0.28±0.23)mm(P<0.05);新生内膜面积分别为(1.09±0.24)mm2和(2.44±1.59)mm2(P<0.05)。上述多项参数在Mytroliums洗脱支架组均显著少于裸支架组。Mytrolimus组新生内膜面积比裸支架组少了55.33%,且Mytrolimus组无一例再狭窄。结论Mytrolimus洗脱支架在置入小型猪冠状动脉4周时可有效抑制内膜增生、预防冠状动脉实验性支架内再狭窄。     

雷公藤内酯醇涂层支架对猪冠状动脉内皮结构和再狭窄的影响

目的观察雷公藤内酯醇涂层支架（triptolide）置入猪冠状动脉后,血管内膜增殖过程中NF-κB、ki67表达的变化,探讨该药物支架对血管内皮的影响。方法将8只猪进行冠状动脉支架置入术,将雷公藤内酯醇涂层支架和裸支架组对照,置入前降支、回旋支、右冠脉近端。术后12周处死动物,采用光镜观察内膜增生情况,扫描电镜观察内皮修复情况,免疫组织化学法检测平滑肌细胞NF-κB、ki67表达。结果术后12周,triptolide组血管内膜增生[(内膜厚度（0.12±0.05）mm]、内膜面积[（1.17±0.25）mm2]明显小于对照组[内膜厚度[（0.35±0.11）mm,P<0.01],内膜面积[（1.81±0.36）mm2,P<0.05];电镜显示血管内膜表面的内皮细胞较对照组分布更紧密,排列更整齐,覆盖更完整;药物组NF-κB、ki67表达量显著低于对照组。结论雷公藤内酯醇涂层支架可抑制猪冠状动脉平滑肌细胞增殖,有效控制局部炎性活动,抑制内膜增殖。     

雌二醇洗脱支架抑制血管内膜增生的实验研究

目的观察雌二醇(E2)洗脱支架植入对高脂喂饲兔腹主动脉内膜增生的影响,并探讨其可能的机制。方法雄兔高脂喂饲后分别于腹主动脉植入裸金属支架、磷酸胆碱(PC)涂层支架和17β-E2洗脱支架,应用HE染色、免疫组化染色及蛋白印迹方法观察17β-E2洗脱支架抑制内膜增生的作用及机制。结果支架植入术后血管壁ERK迅速活化,磷酸化ERK(p-ERK)在术后0.5 h时达峰值。各组支架植入12周时血管内膜均明显增厚。E2洗脱支架组新生内膜面积较裸金属支架组减少36%。支架植入后0.5 h时E2洗脱支架组p-ERK表达明显低于裸金属支架组。2周时E2洗脱支架组内皮化率明显高于裸金属支架组及PC涂层支架组。结论 E2洗脱支架安全、有效,可明显减少实验兔支架植入后的血管内膜增生;与普通裸金属支架对比,E2洗脱支架能够加速支架段血管的再内皮化;丝裂原激活蛋白激酶ERK1/2可能介导了支架植入后血管平滑肌细胞的增殖和内膜增生。     

内皮祖细胞CD34抗体包被冠脉支架对猪冠状动脉再狭窄影响的研究

目的 探讨生物可降解高分子载内皮祖细胞CD34抗体支架是否可降低猪冠状动脉支架置入术后再狭窄.方法 以生物可降解高分子聚乙二醇-聚乳酸-聚谷氨酸共聚物为载体,应用N-琥珀酰亚胺基-3-(2-吡啶二硫)-丙酸酯(SPDP)方法制成内皮祖细胞CD34抗体洗脱支架.18只猪随机分为三组,即紫杉醇支架组、CD34抗体支架组、裸支架组,每组6只,将紫杉醇支架、CD34抗体支架、裸支架分别植入到各组猪的冠状动脉损伤段,4 w后处死,取出支架段血管行病理学观察及计算机图像分析血管管腔面积、内膜增生面积以及面积狭窄百分比.结果 CD34抗体支架组内膜增生面积较裸支架组减低(P＜0.05),紫杉醇支架组内膜增生面积较裸支架组也减低(P＜0.05),但较CD34抗体支架组无明显差别(P＞0.05).结论 生物可降解高分子载内皮祖细胞CD34抗体支架可明显加速支架置入术后血管内皮修复,降低再狭窄的发生.     

可降解雷帕霉素洗脱支架对猪冠状动脉支架置入术后内膜增生的影响

目的:考察可降解雷帕霉素洗脱支架对冠状动脉支架置入术后近期及远期内膜增生影响.方法:所有24只小型猪随机分为1个月及3个月两部分,每部分再随机分为A、B、C 3小组,每小组4只,分别于左冠状动脉前降支及右冠状动脉置入裸支架、聚合物洗脱支架及雷帕霉素洗脱支架,于术后1个月或3个月后动物处死前行冠状动脉造影,处死后用组织形态学方法观察内膜增生情况.结果:47枚支架均成功地置人24头小型猪的冠状动脉,术后均存活.术后即刻冠状动脉造影显示均通畅,处死前冠状动脉造影显示,1个月部分A组及B组各相关动脉均通畅,而C组有1支冠状动脉完全闭塞;3个月部分各动脉均通畅.形态学分析,与裸支架比较,1个月及3个月结果均显示聚乳酸洗脱支架对内膜增生无刺激作用;1个月结果显示药物支架可使管腔直径增加18.0%(P＜0.05),管腔面积增加22.6%(P＜0.05),面积狭窄百分比减少43%(P＜0.05),内膜面积减少35.1%(P＞0.05);3个月部分结果显示,药物洗脱支架对内膜增生的抑制作用消失,甚至有刺激内膜增生的趋势.结论:以聚乳酸为载体的可降解雷帕霉素洗脱支架在小型猪冠状动脉模型虽能抑制1个月血管内膜增生,但远期效果欠佳,其临床意义有待观察.     

伊贝沙坦洗脱支架预防动脉成形术后再狭窄量效关系

目的 探讨伊贝沙坦洗脱支架预防动脉成形术后再狭窄的量效关系。方法 把雄性新西兰白兔40只分为4组,裸支架组于腹主动脉植入裸金属支架,低剂量组植入200μg伊贝沙坦洗脱支架,中剂量组植入400μg伊贝沙坦洗脱支架,高剂量组植入600μg伊贝沙坦洗脱支架,均随访56日后取出支架作病理检查,测量血管腔面积、内膜面积、平均内膜厚度、狭窄程度。结果 裸支架组血管腔面积小于3个药物支架组（P＜0.05）,低剂量组小于中剂量组和高剂量组（P＜0.05）,中剂量组和高剂量组间无明显差异（P＞0.05）;裸支架组内膜面积、内膜厚度、狭窄程度高于药物支架组（P＜0.05）;而低剂量组高于中剂量组和高剂量组（P＜0.05）,中剂量组和高剂量组之间无明显差异（P＞0.05）。结论 伊贝沙坦洗脱支架预防动脉成形术后再狭窄有量效关系。     

雌激素洗脱支架植入兔腹主动脉对内膜增生及内皮化的影响

目的评价雌激素洗脱支架对在体兔腹主动脉内膜增生及内皮化的影响。方法雄兔高脂喂养制成高脂血症模型后分三组,分别于腹主动脉植入裸金属支架、磷酸胆碱涂层支架和17β雌二醇洗脱支架,前两种支架作为对照。每组18只,各组于术后2、4及12周取出6只兔的支架段腹主动脉,测算支架处血管腔面积、新生内膜厚度和面积及管腔狭窄百分比以评价内膜增生程度。应用免疫组织化学染色法分析各时相支架段血管内膜Ⅷ因子阳性率以评估其再内皮化程度。结果3组不同支架植入后导致的血管损伤积分在各时相基本相同(2.17±0.22、2.18±0.21和2.17±0.19,P>0.05);各组支架植入2周时血管内膜已经增厚,在12周时管腔狭窄均<50%,但12周时雌二醇洗脱支架组新生内膜面积较裸金属支架组减少36%(P<0.01),磷酸胆碱涂层支架组与裸金属支架组相比无明显差别;2周与12周时新生内膜面积比在雌二醇洗脱支架组、磷酸胆碱涂层支架组、裸金属支架组分别为0.77、0.61和0.61(P<0.01)。2周时雌二醇洗脱支架组内皮化率明显高于裸金属支架组及磷酸胆碱涂层支架组(78.4%±2.3%比61.4%±3.4%及62.8%±2.9%,P<0.01),4周时各组血管内膜均接近完全内皮化。结论雌二醇洗脱支架可明显减少血管内支架植入后的内膜增生,加速支架段血管的再内皮化,具有良好的对抗再狭窄的应用前景。     

雷帕霉素-缬沙坦复方药物洗释支架预防支架内再狭窄的实验研究

目的　探讨雷帕霉素 -缬纱坦复方药物洗释支架 (复方药物洗释支架 )对支架植入术后再狭窄的预防作用。方法　对 2 2只雄性新西兰白兔进行腹主动脉拉伤后分别植入复方药物洗释支架 (复方组 )和普通支架 (裸支架组 )各 11只。两组均在术后 8周行血管内超声检查和腹主动脉行造影检查。结果　支架部位血管腔面积裸支架组小于复方组 (P <0 0 1)、支架内增生内膜面积及内膜增生程度裸支架组大于复方组 (P <0 0 0 1)。结论　复方药物洗释支架在动物实验中具有明显预防支架内再狭窄的作用     

蛋白涂层支架携带质粒介导的一氧化氮 合酶基因预防冠状动脉球囊扩张后 再狭窄的实验研究

目的　为评价蛋白涂层金属支架携带质粒介导的诱导性一氧化氮合酶 (iNOS)基因局部转染血管壁 ,预防冠状动脉内血管成形术后再狭窄的效果。方法　金属支架涂层为胶联明胶制成。载体为去内毒素纯化pcDNA3。采用标准球囊导管技术 ,将吸附有质粒介导的人肝脏的iNOS基因(pcDNA3hepiNOS)涂层支架置入小型猪 (n =9)冠状动脉前降支中段 ,以相同方法置入单纯蛋白涂层支架做为对照组 (n =9) ,支架与血管直径之比为 1.1～ 1.3:1。结果　在支架置入后 7d ,RT PCR检测和免疫组织化学染色 ,证实在pcDNA3hepiNOS转染的血管段有iNOSmRNA的表达和iNOS蛋白生成 ,而远离器官则无基因的表达。 3个月时冠状动脉造影显示 :转染pcDNA3hepiNOS组 (n =5 )无再狭窄发生 ,而对照组均发生显著的再狭窄。组织病理学形态分析结果显示 :pcDNA3hepiNOS组新生内膜面积 (1.7± 0 .8)mm2 、平均百分狭窄面积 (2 6 .5± 7.5 ) %、平均管腔狭窄百分数 (4 1.2± 16 .5 ) % ,均较对照组小 ,对照组分别为 (2 .8± 0 .8)mm2 ,P <0 .0 5 ;(94.2± 14.3) % ,P <0 .0 0 1;(88.0± 16 .6 ) % ,P <0 .0 0 1;比较内膜面积 /中膜面积比值 (I/M)治疗组较对照组减少了 5 9.8%。结论　在小型猪模型使用蛋白涂层支架携带纯化质粒介导的iNOS基因可直接导入血管     

Experiment Study Of The Preventive Effects Of Valsartan Eluting Stent On In- stent Restenosis

Objectives Background -Neointima hyperplasia and arterial remodeling are the main mechanisms of restenosis after percutaneous transluminal coronary angioplasty. The successful use of coronary stents neutralizes the acute elastic recoil and improves the remodeling mode with reducing restenosis rate by 10 % . But the in - stent neointima hyperplasia becomes more severe. This study aims to set up model of in - stent restenosis in vivo, and to e-valuate the preventive role of implantation of valsartan eluting stent for restenosis. Methods and Results Twenty - two male New Zealand white rabbits were divided into control group and valsartan group. In-travascular ultrasonic (IVUS) results showed the in-trastent neointimal areas of the control group were larger than those of the valsartan group (P < 0. 01) . The minimal lumen area of control group was smaller than that of the valsartan group ( P < 0. 01). Angiog-raphy results showed the normal lumen diameters were similar between two groups ( P> 0.05) . The lum     

雷帕霉素药物洗脱支架对糖尿病小型猪冠状动脉支架置入后内膜增生的影响

目的:评估雷帕霉素药物洗脱支架(SES)对糖尿病小型猪冠状动脉支架置入后内膜增生的作用.方法:建立链脲菌素诱导的糖尿病小型猪模型(糖尿病组,n=12),随机选取2支冠状动脉置入SES,共计置入24枚支架,术后饲养6个月,与非糖尿病置入SES支架的小型猪模型(对照组,n=12)比较冠状动脉造影、血管内超声及组织切片检查结果.结果:两组动物支架置入冠状动脉分布,术前参照血管直径[糖尿病组:(2.78±0.35)mm,对照组:(2.81±0.29)mm]及术后即刻最小管腔内径[糖尿病组:(2.90±0.42)mm,对照组:(2.89±0.33)mm]均相似(P均>0.05).术后6个月糖尿病组支架内狭窄程度[(35.6±9.2)%和(7.9±3.1)%,P<0.001]、支架内晚期管腔丢失[(0.32±0.09)mm和(0.09±0.04)mm,P<0.001]、新生内膜厚度[血管内超声:(0.35±0.12)mm和(0.11±0.08)mm,P<0.05]及新生内膜面积[血管内超声:(1.29±0.51)mm~2和(0.26±0.11)mm~2,P<0.001;组织切片:(1.24±0.76)mm~2和(0.19±0.08)mm~2,P<0.05]均显著高于对照组.结论:糖尿病小型猪冠状动脉置入SES后内膜增生程度显著高于无糖尿病模型.     

Preventive effects of the heparin-coated stent on restenosis in the porcine model.

The coronary stent reduces acute coronary arterial occlusion and late restenosis during and after coronary intervention. However, stent thrombosis and restenosis are still major limitations in the widespread use of the coronary stent. Local drug delivery using the heparin-coated stent may be a new approach, which reduces the incidence of stent thrombosis and restenosis. In order to evaluate the effects of the heparin-coated stent on stent restenosis, heparin-coated stents were compared with control stents in a porcine coronary stent restenosis model. Stent overdilation injury (stent:artery = 1.3:1.0) was performed with bare Wiktor stents (group I, n = 10) and heparin-coated Wiktor stents (group II, n = 20; HEPAMED, Medtronics) in porcine coronary arteries. Follow-up quantitative coronary angiography (QCA) was performed at 4 weeks after stenting, and histo-pathologic assessments of stented porcine coronary arteries were compared in both groups. On QCA, percent diameter stenosis was significantly higher in group I than in group II (16.3% +/- 6.62% vs. 9.6% +/- 5.06%, P < 0.05). The injury score of stented porcine coronary arteries was the same in both groups (1. 26 +/- 0.23 vs. 1.20 +/- 0.22). The area of pathologic stenosis of the stented arteries was higher in group I than in group II (41.6% +/- 12.5% vs. 27.1% +/- 9.9%, P < 0.005). The neointimal area was higher in group I than in group II (4.58 +/- 1.41 mm(2) vs. 2.57 +/- 1.07 mm(2), P < 0.05). By immunohistochemistry, the proliferating cell nuclear antigen (PCNA) index was higher in group I compared with group II (11.2% +/- 6.75% vs. 6.3% +/- 4.14%, P < 0.05). The heparin-coated stent is effective in the prevention of late coronary stent restenosis in a porcine coronary stent restenosis model. This may be related to the inhibition of neointimal cell proliferation.     

Local Delivery of C-myc Antisense Oligodeoxynucleotide by Gelatin Coated Platinium-Iridium Stent to Prevent Restenosis in a Normal Rabbit Carotid Artery

Restenosis occurred in 30%-40% of percutaneoustransluminal coronary angioplasty (PTCA). It isthought that vascular elastic recoil, remodeling,thrombosis and smooth muscle cells (SMCs)proliferation play a key role in the pathogenesis ofrestenosis. Because intracoronary stents avoided elasticrecoil and remodeling, it can significantly decreaserestenosis. However, in-stent restenosis remains amajor problem, occuring in 15% -20% of theseprocedures [1].How to prevent restenosis has been to amajo…     

Angiopeptin-eluting stents: observations in human vessels and pig coronary arteries

Local drug delivery from polymer-coated coronary stents may reduce the incidence of in-stent restenosis. Angiopeptin, an inhibitor of smooth muscle cell proliferation, may reduce the clinical impact of restenosis. The objectives of this study were to characterize the release kinetics and distribution of angiopeptin-loaded phosphorylcholine (PC)-coated drug delivery (DD) BiodivYsio stents and assess their safety and efficacy at reducing neointima formation. I125-angiopeptin-loaded DD-PC-coated stents were implanted into human saphenous vein segments ex vivo, and I125 angiopeptin was detected in the medial layer at 1 hour. When implanted in pig coronary arteries, I125 angiopeptin was found adjacent to the stent at intervals up to 28 days. No significant amounts were found elsewhere. To assess efficacy, twelve angiopeptin-loaded DD-PC-coated stents, twelve non-loaded DD-PC stents, ten standard PC-coated stents and 8 uncoated stents were implanted into normal porcine coronary arteries. Stents were harvested at 28 days and neointima formation was assessed by computerized morphometry. No adverse tissue reactions were seen with any of the PC-coated stents. No significant differences were seen in neointimal or luminal cross-sectional areas between study groups. Local delivery of I125 angiopeptin into the vascular wall can be achieved using a PC-coated stent. Delivery of angiopeptin from drug delivery PC-coated stents is safe, but does not lead to a significant reduction in neointimal growth at 28 days within the parameters of this study.     

Atorvastatin stent coating does not reduce neointimal proliferation after coronary stenting

PURPOSE: Statins seem to be suitable for restenosis prevention via reduction of smooth muscle cell proliferation, anti-inflammatory effects, and improvement of endothelial function. The aim of the present study was to test the efficacy of an atorvastatin stent coating for restenosis inhibition in the porcine coronary stent model. METHODS AND RESULTS: Twenty stents (BiodivYsio Matrix LO, uncoated or with 56 microg atorvastatin load) were implanted in LAD and CX coronary arteries of 10 domestic pigs with an over stretch ratio of 1.25. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment group. After 28 days, there was no significant difference in parameters describing in-stent restenosis (neointimal area 3.14 +/- 1.13 mm(2) [control] vs. 3.12 +/- 1.07 mm(2) [atorvastatin stent]; p = 0.978). However, there was a trend towards a lower degree of inflammation in the atorvastatin stent group. CONCLUSION: Atorvastatin stent coating showed a trend towards reduced local inflammation near the stent struts, but could not reduce neointimal formation in the porcine coronary over stretch model.