血管内照射、抗血小板药物和他汀类药物联用预防再狭窄的实验研究

Experimental study of intravascular irradiation phus clopidogel and simvastatin on restenosis

目的:观察血管内照射、抗血小板药物—氯吡格雷和他汀类药物—辛伐他汀联合应用对再狭窄的预防作用,分析这几种方法之间是否存在协同作用。方法:采用雄性新西兰白兔,给予高脂、高胆固醇饲料喂养6周后,行髂动脉内膜损伤术复制再狭窄模型。然后随机分成4组:单纯损伤组、照射组、药物组、联合组。在术后2、4和8周3个时相点用免疫组化方法检测血管壁增殖细胞核抗原(PCNA)表达阳性细胞,即增殖细胞;以及核因子κB(NF-κB)和细胞间黏附分子-1(ICAM-1)的表达;用计算机图像分析法观察血管组织形态学的变化,并对免疫组化结果进行定量分析。结果:1.其它3组与单纯损伤组相比:①表示内膜增殖程度的指标:内膜厚度(IT)、内膜/中膜厚度(IT/MT)、内膜面积(IA)、内膜面积/中膜面积(IA/MA)和管腔面积(LA)均显著减少(P<0.05);②血管壁增殖细胞PCNA及NF-κB、ICAM-1的表达均显著降低(P<0.05)。2.其它3组与联合组相比:①表示内膜增殖程度的指标IT、IT/MT、IA、IA/MA、LA均显著减少(P<0.05);②血管壁增殖细胞PCNA及NF-κB、ICAM-1的表达均显著降低(P<0.05)。结论:1.抗血小板药物—氯吡格雷和他汀类药物—辛伐他汀联合应用可以防止再狭窄的形成;2.血管内照射可有效地防止血管成形术后再狭窄的形成;3.联合应用血管内照射和辛伐他汀与氯吡格雷进行干预效果更加明显。

AIM： To evaluate the preventive effects of intravascular in＇adiation phus clopidogel and simvastatin on restenosis, and to analyze their synergy. METHODS： Male New Zealand rabbit models of restenosis were developed. They were divided into 4 groups ： the control group （without any treatment）, intravascular in＇adiation group （ ionizing radiation using liquid 32p-filled balloon catheter） , drug group （clopidogel and simvastatin） and combination group （ionizing in-adiation combined with clopidogel and simvastatin）. At week 2, 4 and 8 after the balloon injury operation, the target vascular sections were cut and stained with HE and histomorphologic changes of the vessels were carefully observed using computer analysis of photomicrograms. ICAM-1, NF-kB and PCNA expressions were detected by inmunohistochem- ical technique. RESULES： Intravascular irradiation treatment significantly inhibited neointimal proliferation. Compared with the control group ： lumen area（LA） , intimal thickness （ IT）, intimal area（ IA）, and IT/MT and IA/MA ratios of were significantly reduced in a dose-dependent manner（ P 〈 0.05 ） , and PCNA, NF-kB and ICAM-1 expression was also significantly reduced （P 〈 0.05）. Compared with combination group： LA, IT, IA, IT/MT and IA/MA of the drug and in＇adiation group were significantly reduced in a dose-dependent manner（P 〈 0.05）, and PCNA, NF-kB and ICAM-1 expressions were significantly lower （ P 〈 0.05 ）. CONCLUSION ： Restenosis can be prevented either by clopidogrel and simvastatin or by intravascular irradiation, while intravascular irradiation combined with medication can exert much better synergistic effects.