Triptolide涂层支架对猪冠脉内膜增殖及血管内皮生长因子、细胞间黏附分子-1表达的影响

目的 研究雷公藤内酯醇涂层支架(triptolide eluding stent,TES)置入猪冠状动脉后对血管内膜增生、炎性因子激活、血管损伤、术后再狭窄的影响及支架的安全性.方法 12只健康小型猪随机分为3组,分别植入雷公藤内酯醇涂层支架(100μg)、雷帕霉素洗脱支架(parter)、裸金属支架(每组12枚).每只猪冠状动脉前降支、回旋支、右冠状动脉各植入一枚支架,术后给予抗血小板药物,12周后复查冠状动脉造影(QCA)分析管腔变化、组织病理、血常规、生化结果,免疫组化榆测支架处血管VEGF,ICAM-1,α-actin的变化.结果 各组支架植入顺利,12周内无死亡,血管损伤积分无差异,管腔内均无血栓形成.裸支架组支架部位血管腔面积(3.76±0.61)mm2、最小管腔内径(2.15±0.18)mm小于TES组[(5.13±0.46)mm2,(2.65±0.21)mm]和DES组[(5.01±0.54)mm2,(2.65±0.25)mm,P＜0.01];裸支架内增生内膜面积及内膜增生程度裸支架组大于TES组和乐普支架组(P＜0.05),裸支架组支架部位血管内膜VEGF,ICAM-1,α-actin表达明显强于TES和乐普支架组.支架植入前后各组动物血细胞计数和肝肾功能无明显变化.结论 雷公藤内酯醇洗脱支架能抑制血管新生内膜增殖和炎性因子的表达,在支架植入12周后能有效地预防再狭窄.     

生物可降解性基因释放血管内支架抑制小型猪肾动脉球囊扩张后c-myc基因表达及内膜增生的实验研究

目的　研究释放ASODN基因片段的生物可降解血管内支架在抑制小型猪肾动脉球囊损伤后c-myc基因表达及内膜增生中的作用。方法将ASODN涂层BES与裸BES分别植入到16只实验小型猪球囊扩张后的双侧肾动脉内，分别在术后24h、1周、4周及12周各处死4只动物；用Western　Blot法进行c-myc基因蛋白表达分析；病理分析对两种支架不同时期的内膜厚度、内膜面积、管腔面积及PCNA染色增殖指数进行比较。结果ASODN涂层BES及裸BES置入段血管在损伤后12周内均表现出连续的内膜愈合与生长过程；支架置入后24h，ASODN涂层BES置入段血管表达c-myc蛋白与健康肾动脉相似，均明显低于裸支架置入段血管，差异持续至术后4周；12周时，各组c-myc蛋白表达差异消失，裸BES、ASODN涂层BES置入段血管及健康肾动脉c-myc蛋白均呈微弱表达。除24h外，ASODN涂层BES各期内膜增生程度均较裸BES弱，以支架周围明显，管腔面积均大于裸BES组，PCNA指数均小于裸BES组（P〈0．05）。结论ASODN涂层BES能有效抑制小型猪肾动脉球囊损伤后c-myc基因蛋白表达，损伤后12周内表现出对新生内膜增生较强的抑制作用，使用PI，LA材料制作的BES是基因释放的良好载体。     

类细胞膜仿生药物缓释涂层冠状动脉支架材料

背景:金属冠状动脉支架植入后发生再狭窄的概率高达20%～30%,为了降低再狭窄发生率,在863项目支持下,探索新型药物涂层支架治疗冠状动脉狭窄的可能性.目的:将约物涂层支架植入小猪冠状动脉狭窄模型,观察其安全性和有效性,以及与金属裸支架的差异性.设计、时间及地点:随机对照,动物实验于2003-11/2004-04在阜外心血管病医院完成.材料:由单体2-(甲基丙烯酰氧基)乙基-2-(三甲基氨基)乙基磷酸酯、甲基丙烯酸十八酯、甲基丙烯酸羟丙酯和甲基丙烯酸(三甲氧)硅基丙酯合成了一种新型类细胞膜涂层材料.方法:21只猪随机分为3组:裸支架组,涂层携载雷帕霉素(120 μ g,支架)组,单纯涂层支架组.将支架预装到输送系统,使用Toshiba CSⅡ型C臂成像仪造影条件下,将药物支架置入小型猪冠状动脉血管,每只猪置入2枚支架.主要观察指标:使用图像分析仪检测管腔直径,管腔面积,支架上平均内膜厚度,支架间平均内膜厚度,内膜面积,面积再狭窄百分比,损伤指数.结果:置入后28 d时,涂层携载雷帕霉素组和裸支架组相比,支架上内膜厚度、支架间内膜厚度、新生内膜面积差异均有显著性意义(P＜0.05),其中新生内膜面积涂层携载雷帕霉素组比裸支架组减少了44.87%:虽面积狭窄百分比差异无显著性意义,但P值(0.053)接近0.05;且涂层携载雷帕霉素组无再狭窄发生.结论;涂层携载雷帕霉素支架可显著抑制支架置入后血管内膜增生和再狭窄发生.     

雷公藤内酯醇洗脱支架对小型猪冠状动脉内膜增生及细胞分裂周期基因2、基质金属蛋白酶2表达的影响

目的探讨雷公藤内酯醇药物洗脱支架抑制再狭窄的机制。方法 18只健康国内西藏小型猪随机分为不锈钢裸支架组(BMS)、雷帕霉素洗脱支架组(SES)、雷公藤内酯醇洗脱支架(TES)100μg组,每组各6只猪,术后7 d和28 d复查冠状动脉造影后放血处死动物,分离冠状动脉支架血管段固定。测定冠状动脉外弹力膜层横断面积、支架上平均内膜厚度、支架间平均内膜厚度,观察血管平滑肌细胞的移行、增殖及内膜厚度变化,计算血管损伤积分。用免疫组织化学方法检测冠状动脉组织中基质金属蛋白酶2(MMP2)和细胞分裂周期基因2(CDC2)的蛋白表达,并进行半定量分析。结果支架植入导致的冠状动脉血管损伤积分各组均差异无统计学意义(P=0.457)。支架植入后7 d,BMS组可见增生内膜几乎全部包绕支架撑杆,SES组、TES 100μg组支架撑杆两侧可见内膜增生,管腔面支架裸露。支架植入28 d后各组血管内膜完全内皮化,BMS组支架上内膜厚度、支架间内膜膜厚度均较TES 100μg、SES组厚,差异有统计学意义(P0.01)。支架植入后7 d和28 d,免疫组织化学分析MMP-2、CDC2激酶在BMS组中强表达,TES 100μg和SES组弱表达,平均灰度值经统计学比较,差异有统计学意义(P0.01)。结论:雷公藤内酯醇洗脱支架100μg组剂量能很好的抑制血管内膜过度增生,预防再狭窄。     

缬沙坦涂层支架置入兔腹主动脉对血管内膜胶原沉积及AT2受体表达的影响

背景:有实验证实口服缬沙坦能降低血管支架置入后血管再狭窄的发生,局部应用缬沙坦能否产生相同的效应且其可能的作用机制需验证.目的:采用缬沙坦涂层支架置入实验兔腹主动脉,观察支架对血管狭窄情况、新生内膜中胶原沉积及AT2受体表达的影响.设计:随机对照动物实验.单位:北京市友谊医院.材料:实验于2004-10/2006-03在北京市友谊医院实验室完成,选用15只新西兰大白兔,雌雄不拘,体质量2.75～3.2kg,由北京友谊医院动物实验室提供.动物实验室喂养适应1周.实验过程中对动物的处置符合动物伦理学标准.缬沙坦粉剂由诺华公司馈赠,MASSON染色试剂为北京友谊医院病理科提供,1%天狼星红苦味酸溶液为中日友好医院病理科提供,鼠抗兔AT2单克隆抗体为美国Santa Cruz Biotechnology公司产品,Envision试剂购自Dako公司,引物由北京赛百盛公司合成.方法:①随机数字表法将实验兔分为裸支架组、载体涂层支架组及药物涂层支架组,每组5只,分别在实验兔腹主动脉的肾动脉开口下方植入裸支架、载体涂层支架及药物涂层支架.②支架置入前后即刻及置入后3个月分别行腹主动脉造影测量腹主动脉直径.③3个月后麻醉处死实验兔.取支架血管段切片并作苏木精一伊红染色,对管腔面积、内外弹力膜围绕面积、新生内膜面积及最大内膜厚度进行测定.④将支架血管段进行MASSON染色,观察胶原沉积情况,天狼星红苦味酸染色进一步观察胶原的类型.⑤免疫组化方法检测AT2受体蛋白质表达,并采用RT-PCR方法测定AT2受体mRNA的表达.主要观察指标:①不同时间腹主动脉直径测定结果.②支架血管段管腔面积、内外弹力膜围绕面积、新生内膜面积及最大内膜厚度.③支架血管段胶原类型及沉积情况.④AT2受体蛋白质及mRNA表达.结果:纳入实验兔15只,裸支架组1只在支架置入过程中死亡,载体涂层支架组1只在饲养过程中死亡,其余13只均进入结果分析.①各组实验兔支架置入前后即刻及术后3个月组间比较结果显示血管直径差异无统计学意义(P＞0.05).②缬沙坦组实验兔管腔面积大于裸支架组及载体支架组,差异有显著性意义(P＜0.01),新生内膜厚度及新生内膜面积均小于裸支架组及载体支架组,差异有显著性意义(P＜0.01).③MASSON染色显示裸支架组及载体涂层支架组新生内膜中胶原大量沉积,缬沙坦洗脱支架新生内膜中胶原沉积较少;天狼星红-苦味酸染色经偏光显微镜下可见生内膜中主要是Ⅲ型胶原沉积,在支架脚附近间或有Ⅰ型胶原的沉积,缬沙坦涂层支架组Ⅲ型胶原沉积明显减少.④裸支架组与载体涂层支架组AT2受体蛋白仅在外膜表达,缬沙坦药物涂层支架AT2受体蛋白自外膜至内膜均有表达,药物涂层支架组AT2受体/β-Actin表达高于载体支架组及裸支架组(P＜0.01).结论:缬沙坦涂层支架能通过减少胶原尤其是Ⅲ型胶原的沉积抑制支架术后血管内膜增生,其机制可能与缬沙坦涂层支架上调AT2受体表达有关.     

口服雷帕霉素抑制哺乳动物雷帕霉素靶蛋白(mTOR)防治支架内再狭窄的实验研究

目的 联合应用血管内超声(IVUS)、病理学及免疫组织化学技术,探讨口服雷帕霉素抑制支架内再狭窄的作用及其分子机制.方法 通过球囊损伤腹主动脉和高脂(1％胆固醇)饲料喂养雄性新西兰纯种兔8周,然后将其分为裸支架组(BMS)、裸支架+口服雷帕霉素组(BMS+ RAPA)和雷帕霉素药物涂层支架组( DES),每组8只.继续高胆固醇饲料喂养4周后,应用IVUS检测各组实验兔支架置人前后腹主动脉病变部位管腔最小直径(MLD)、血管外弹力膜面积(EEMA)、管腔面积(LA)、斑块面积(PA)及斑块负荷(PB),并计算管腔丢失量.病理学观察支架内增生组织的病理学形态改变,免疫组织化学检测哺乳动物雷帕霉素靶蛋白(mTOR)在局部斑块中的表达情况.结果 IVUS结果显示BMS+RAPA组及DES组的PA、PB均明显小于BMS组(P均＜0.01),而MLD明显高于BMS组,支架植入4周后管腔丢失明显小于BMS组(P均＜0.05);病理学检测显示BMS组支架植入后内膜增生明显,管腔面积狭窄率明显大于BMS+RAPA组及DES组.BMS+RAPA组及DES组的斑块局部mTOR表达明显低于BMS组.结论 口服雷帕霉素通过抑制mTOR抑制斑块生长,降低支架内再狭窄;口服雷帕霉素配合裸支架与雷帕霉素药物支架抑制支架内再狭窄的作用相似.     

一种新型聚合物携带雷帕霉素洗脱血管支架抑制内膜增生的效应

背景:课题组前期已进行了系列体内生物相容性实验,证实了聚砜-聚氧化乙烯共聚物材料具有良好的细胞相容性、血液相容性、组织相容性和使用安全性.目的:在前期实验基础上进一步评价聚砜-聚氧化乙烯共聚物作为携带雷帕霉素涂层的新型血管支架抑制血管内膜增生防治再狭窄的安全性及有效性.设计、时间及地点:随机对照动物实验,于2007-01在东南大学附属中大医院心内科完成.材料:采用超声雾化的方法将含聚氧化乙烯30%的聚砜-聚氧化乙烯共聚物均匀喷涂于316 L不锈钢金属裸支架上 ,制成含雷帕霉素130 合μg的涂层支架,由汀苏省微纳生物医疗器械重点实验室制作;金属裸支架采用相同材质和结构制作.方法:通过球囊扩张小型猪冠状动脉形成冠状动脉狭窄模型.6只小型猪随机抽签法分为2组,实验组置入雷帕霉素洗脱支架;对照组置入金属裸支架,每组3只.置入后第28天行冠状动脉造影和血管内超声检查.主要观察指标:支架置入后冠状动脉管腔丢失情况、新生内膜面积和厚度、内皮生长情况;免疫组织化学分析测定增殖细胞核抗原;TUNEL法检测血管平滑肌细胞凋亡数;扫描电镜观察内皮细胞的覆盖情况.结果:血管支架置入后第28天冠状动脉造影检查显示,实验组血管腔直径丢失及直径狭窄率较对照组明显减少(P<0.05).病理学证实,实验组较对照组管腔面积增加、支架内新生内膜面积和面积再狭窄率减小(P<0.05).对照组增殖细胞核抗原细胞阳性率较实验组明显减少(P<0.05),单位面积内血管平滑肌细胞凋亡数明显增加(P<0.05).扫描电镜显示对照组支架置入28 d血管内皮细胞完全覆盖,实验组基本覆盖.结论:在小型猪/冠状动脉支架置入模型中,聚砜-聚氧化乙烯共聚物携带的雷帕霉素洗脱血管支架显示出良好的安全性和降低冠状动脉再狭窄的有效性.     

PEG-PLA-PGL／RGD 涂层支架对冠脉支架置入术后再狭窄的影响

目的 探 PEG-PLA-PGL/RGD 涂层支架置入后对猪冠状动脉内皮化及内膜增生的影响。方法 以 PEG-PLA-PLG 聚脂肪酸为载体,通过载体接枝精氨酸-甘-天冬氨酸三肽聚合物（RGD）,制成生物可降解高分子载 RGD冠脉支架。实验分为裸支架组、紫杉醇涂层支架组、PEG-PLA-PGL/RGD 涂层支架组,每组实验小型猪6只,将相应支架分别置入到每组猪的冠状动脉损伤段,分别4周及12周后处死,取出支架段血管行病理学观察及计算机图像分析测定管腔面积（lumen area,LA）、内弹力膜面积（internal elastic membrane area,IEMA）,并根据 LA 及 IEMA 计算出新生内膜面积（neointima area,NA）及面积狭窄百分数（percentage of area stenosis,％AS）。结果 PEG-PLA-PGL/RGD 涂层支架组内膜增生面积较裸支架组明显减低（P ＜0．05）,PEG-PLA-PGL/RGD 涂层支架组内膜增生面积与紫杉醇涂层支组无明显差别（P ＞0．05）。结论 PEG-PLA-PGL/RGD 涂层支架较裸支架,可明显加速内皮修复,明显降低再狭窄的发生,是一极具前景研究方向。     

雷帕霉素释放生物可降解性血管内支架预防小型猪肾动脉球囊损伤后内膜增生的实验研究

目的 究雷帕霉素释放生物可降解性血管内支架在抑制小型猪肾动脉球囊损伤后内膜增生中的作用。方法将雷帕霉素释放BES与裸BES分别植入到6只实验小型猪球囊扩张后的双侧肾动脉内，8周后处死进行病理学观察，对两种BES的内膜厚度、内膜面积、管腔面积及PCNA染色增殖指数进行比较。结果8周时所有BES在血管内展开良好，雷帕霉素释放BES内膜厚度、内膜面积明显小于裸BES，管腔面积明显大于裸BES，PCNA指数明显小于裸BES（P〈0．05）。结论BES能完成血管内支撑任务；与裸BES相比，雷帕霉素释放BES能有效抑制小型猪肾动脉球囊损伤后血管内膜增生。     

紫杉醇可降解内支架防治犬血管再狭窄的免疫组化分析

目的　评做携带抗增生药物紫杉醇的生物可降解性血管内支架 (BIS)防治血管再狭窄的效果。方法　以乙交酯 丙交酯共聚物 (PLLGA)为原料分别制备携带紫杉醇的BIS和未携带药物的BIS(裸BIS)。球囊扩张法建立犬双侧骼外动脉再狭窄动物模型 ,将 8对紫杉醇BIS和裸BIS分别植入到 8只犬的双侧骼外动脉内 ,6周后处死实验动物完整取出支架段血管行病理学观察及免疫组化评价。结果　裸支架组血管平均管腔面积小于紫杉醇支架组血管平均管腔面积 (775 86 μm2 vs113435 μm2 ,P <0 0 1)。裸支架组血管新生内膜平均增生面积大于紫杉醇组平均内膜增生面积(2 4 80 3μm2 vs 113435 μm2 ,P <0 0 1) ;裸支架组PCNA细胞阳性率高于紫杉醇支架组 (38%± 15 %vs 11%± 0 31% ,P <0 0 1) ,两组具有显著统计学差异。结论　生物可降解性血管内支架作为载荷和释放药物的有效平台 ,通过所携带抗增生药物紫杉醇可以显著地抑制VSMC增殖和血管内膜的增生是防治血管再狭窄的新策略和理想手段。对于BIS的精确释放速率、紫杉醇预防再狭窄的适合剂量以及BIS的远期效果还需进行大量深入的研究     

Response of renal and femoropopliteal arteries to Palmaz stent implantation assessed with intravascular ultrasound.

PURPOSE: To establish the processes responsible for late lumen loss in renal and femoropopliteal Palmaz stents using intravascular ultrasound (IVUS). METHODS: The first 7 consecutive patients treated with stents for renal (n = 4) and femoropopliteal (n = 3) arterial occlusive disease were studied with IVUS immediately after angiographically successful stent placement (< 10% residual stenosis) and periodically during follow-up. Images of both stent edges and the most stenotic site inside the stent at followup were matched to the same cross sections captured immediately after stent placement for quantitative analysis. RESULTS: Late lumen loss in renal artery stents at 5 to 34 months was considerably less than in femoropopliteal stents (17% versus 62%, respectively). In the renal location, late lumen loss (3.0 +/- 1.3 mm2) was due to neointimal hyperplasia, whereas stent area remained unchanged (3% decrease). Late lumen loss (7.4 +/- 8.2 mm2) in femoropopliteal stents was due to neointimal hyperplasia and stent area reduction (26%). Overall, in both types of arteries, neointimal development and stent area reduction were larger at the most stenotic site than at the stent edges. CONCLUSIONS: These data suggest that there may be differences between renal and femoropopliteal arteries in the extent of hyperplastic response to stents.     

Biocompatibility of tetramethylpyrazine-eluting stents in normal porcine coronary arteries.

OBJECTIVE: Drug-eluting stents have been used to markedly decrease in-stent restenosis in 6 months, but they are noticed due to the late thrombogenicity. The purpose of the present study was to evaluate the biocompatibility of Tetramethylpyrazine-eluting stents by investigating the intimal response and thrombogenicity in normal porcine coronary arteries by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS) and histomorphometry. METHODS: Bare metal stents (BMS) were uniformly spray-coated with Tetramethylpyrazine (TMP 200 microg) and prepared for TMP-eluting stents (TES). Fourteen coronary arteries in 14 pigs underwent stent implantation. Seven TES were implanted in 7 pigs and 7 BMS in other 7 pigs. The stents were deployed with a stent-to-artery ratio of 1.1-1.2/1.0 in order to induce vascular wall injury. QCA and IVUS were performed before and immediately after the implantations and at 28 days (end time point). The analysis on blood cell count, biochemical parameters, status of behavior of pigs were evaluated before the implantation and at the time of 1 and 28 days. Stented-coronary arteries, stented-coronary arteries related ventricular wall, lung, liver and kidney were harvested after euthanasia of animals at the endpoint. Histopathology and histomorphometry had been done to assess the local toxicity of TES to these organs. RESULTS: All the stents were successfully implanted, however, 4 pigs died of cardiac tamponade or anesthesia. No bone marrow depression and hemolysis was seen. No damage to the function and metabolism of liver and kidney was discovered. No thrombosis was found in control and test groups. Few inflammatory cells were found in the stented-coronary artery walls at each endpoint in both groups. No damage to stented-coronary arteries related ventricular wall, lung, liver and kidney was detected due to TES implantation. Compared with the control group, the neointimal area was significantly reduced in the TES group (60.2+/-23.5% vs 10.0+/-2.1%, P=0.01) by IVUS analysis, but the lumen area in the TES group was increased (4.34+/-0. 93 mm(2) vs 1.29+/-1.02 mm(2), P=0.011), the neointimal area was reduced markedly (1.51+/-0.45 mm(2) vs 4.60+/-1.39 mm(2), P=0.004). CONCLUSIONS: The biocompatibility of TES in porcine model at 28 days seems to be good and acceptable. Biocompatibility can be evaluated by IVUS and histopathology in a porcine restenosis model.     

血管内超声分析重复支架术有或无联合冠脉内放疗对患者支架内再狭窄复发的作用

目的　系列血管内超声 (IVUS)分析重复支架术 (RS)有或无联合冠脉内的放射治疗 (IRT)对支架内再狭窄 (ISR)患者再狭窄复发的作用。方法　 99例 ISR的患者经 RS治疗后随机分为 1 92 Ir放疗组 (n=5 7)和对照组 (n=4 2 ) ,行系列冠脉造影和 IVUS检查 ,分别测量支架、管腔及增生内膜的面积和容积。结果　随访 6月 ,冠脉造影显示放疗组较对照组再狭窄复发率低。两组基线和随访的支架最小面积、平均面积和容积均无变化。两组在随访 6月支架最小腔内面积、平均腔内面积和管腔容积均减小 ,平均增生内膜面积和增生内膜容积均增加 ,但对照组比放疗组的变化更明显。结论　系列 IVUS证实 :IRT抑制新生的内膜形成 ,RS联合 IRT较 RS不联合 IRT更有效减少患者的 ISR复发     

Assessment of potential relationship between wall shear stress and arterial wall response after bare metal stent and sirolimus-eluting stent implantation in patients with diabetes mellitus

BACKGROUND: Wall shear stress (WSS) has been associated with neointimal hyperplasia (NIH) following bare metal stent (BMS) implantation. Drug-eluting stents (DES) almost abolish NIH. Conversely, diabetes mellitus amplifies NIH response. The association between WSS and arterial wall response following DES and BMS implantation in diabetic patients remains to be evaluated. METHODS: The study involved 20 diabetic patients randomized to BMS (n = 9) or sirolimus-eluting stent (SES; n = 11) implantation in native coronary arteries. A computational fluid dynamic model applied 3D intravascular ultrasound (IVUS) and two-plane angiographic to measure WSS (Pa). IVUS assessments were performed post-procedure and at 9-months follow-up. The target segment encompassed the stent plus 5 mm distal and proximal edges. A total of 93 subsegments were evaluated: in-stent segments divided in three subsegments (proximal, mid and distal; n = 60) and proximal and distal edges (n = 33). RESULTS: Stent length was similar between BMS (17.4 +/- 7.3 mm) and SES (19.8 +/- 6.8 mm) groups. NIH was observed in all BMS subsegments (n = 27) versus one subsegment in the SES group (n = 33). WSS ranged from 0.52 to 4.20 Pa in the BMS and from 0.42 to 3.06 Pa in the SES group. There was no correlation between WSS and NIH in either stent group. In addition, there were no correlation between the change of external elastic membrane (EEM) or plaque growth at the edges and WSS. CONCLUSION: WSS was not associated with NIH after implantation of SES or BMS in diabetic patients. Plaque growth or the change of EEM at the edges were not associated with WSS either.     

聚甲基丙烯酸丁酯／纳米二氧化硅涂层支架的生物相容性研究

目的评价不锈钢支架聚甲基丙烯酸丁酯,纳米二氧化硅涂层的生物相容性。方法聚甲基丙烯酸丁酯,纳米二氧化硅涂层支架与裸金属支架分别置入犬冠状动脉回旋支,每组9只,术后4周时行冠状动脉造影及组织病理学分析,涂层组支架置入前与置入后4周采集血清样本做肝肾功能检测。结果两组犬4周时冠状动脉造影显示支架段管腔狭窄,无血栓形成、栓塞及动脉瘤,光学纤维镜下未见内膜下出血和中层坏死,无附壁血栓,无明显炎症细胞浸润;扫描电子纤维镜显示所有支架段血管基本内皮化,管壁无血小板和纤维蛋白沉积。两组犬损伤积分差异无统计学意义（P〉0．05）,新生内膜厚度、管腔面积、管腔面积狭窄率及内膜平滑肌细胞百分率比较差异无统计学意义（P〉0．05）,涂层支架置入后与置入前比较对肝肾功能无明显影响（P〉0．05）。结论不锈钢支架聚甲基丙烯酸丁酯,纳米二氧化硅涂层具有良好的生物相容性,不引起严重的局部组织反应,可用于药物洗脱支架的制作。     

Reduction of neointimal hyperplasia in porcine coronary arteries by 2-deoxy-d-glucose

Background

The drug eluting stents have been shown to play a substantial role in preventing in-stent restenosis. This study was initiated to determine the efficacy of 2-deoxy-d-glucose (2-DG) in an in-stent restenosis model for reducing neointimal hyperplasia after coronary stent placement.

Methods

In a porcine overstretch model, three kinds of stents were investigated (n = 12 per group): bare metal stents (BMS), rapamycin-eluted stents (RES), and BMS after intracoronary short-term application of 2-DG (DGS). After 42 days histomorphometric and histopathological analyses were performed.

Results

Neointimal thickness (BMS: 0.38 ± 0.08, RES: 0.24 ± 0.11, DGS: 0.15 ± 0.01), area stenosis (BMS: 47.39 ± 2.76, RES: 32.2 ± 2.08, DGS: 29.30 ± 2.98) did not differ after 42 days between the RES and DGS but were significantly lower as compared to BMS only. Lumen area (BMS: 3.15 ± 1.53, RES: 4.37 ± 1.72, DGS: 4.77 ± 2.14) was significantly higher in the DGS group in comparison to the BMS group. The calculated injury and inflammation scores were similar and re-endothelialization was confirmed in all groups.

Conclusions

This study could demonstrate that in porcine stent model neointimal hyperplasia and re-endothelialization after application of 2-DG are comparable to those seen in RES. Thus, 2-DG might be a promising clinical application for coronary stent coating.