口服雷帕霉素抑制支架内再狭窄的血管内超声的实验研究

Rapamycin to prevent artery restenosis after stent implantation:an intravascular ultrasound study

目的应用血管内超声(IVUS)观测口服雷帕霉素抑制支架内再狭窄的作用。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,然后将其分为对照组、口服雷帕霉素组、裸支架组、裸支架+口服雷帕霉素组和雷帕霉素药物涂层支架组,每组8只。口服雷帕霉素每天0.5 mg/kg或支架干预4周。检测动脉粥样硬化造模前后及干预前后的血脂指标,应用IVUS检测各组实验兔支架置入前后及用药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),并计算管腔丢失、斑块负荷(PB)、斑块的偏心指数(EI)及血管的重构指数(RI)。通过比较各组IVUS指标,明确口服雷帕霉素抑制支架内再狭窄的作用。结果 与对照组及裸支架组比较,口服雷帕霉素组、裸支架+口服雷帕霉素组以及雷帕霉素涂层支架组的血脂指标未见明显降低。口服雷帕霉素组、裸支架+雷帕霉素组、雷帕霉素药物支架组的PA、PB均明显小于对照组和裸支架组(P均<0.01);裸支架+雷帕霉素组、雷帕霉素药物支架组的MLD明显高于裸支架组,管腔丢失明显小于裸支架组(P均<0.05),而裸支架+雷帕霉素组、雷帕霉素药物支架组未见明显差异。结论 口服雷帕霉素能够抑制斑块生长、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的作用相似。

Objective To identify the effect of oral administered rapamycin on the prevention of restenosis after stent implantation with intravascular ultrasound（IVUS）. Methods Forty New Zealand White rabbits underwent balloon-induced abdominal aortic wall injury and were given a diet of 1% cholesterol for 8 weeks. Then, they were divided into five groups： the control group, the oral rapamycin group（ RAPA group）, the bare metal stent group（ BMS group）, the bare metal stent with oral rapamycin group（BMS ＋ RAPA group） and the rapamycin eluting stent group（DES group）. Rabbits in the RAPA and BMS ＋ RAPA groups received a daily oral dose of rapamycin（0.5 mg/kg）, whereas rabbits in other groups received no medications. All the rabbits were euthanized after the 4-week intervention. Serum lipids were measured and intravascular ultrasound（IVUS） was performed. The minimal luminal diameter（ MLD）, external elastic membrane（EEM） area, lumen area（LA）, and plaque area（ PA）, plaque burden（PB） were measured, and the lumen eccentricity index, remodeling index and lumen reduction were calculated. Results After the 4-week intervention, there was no significant difference of serum lipid levels among the five groups. Oral administration of rapamycin in the RAPA and BMS ＋ RAPA groups showed similar effects in reducing PA and PB as the DES group, which all were better than the control and BMS group. The BMS ＋ RAPA group and DES group showed much more MLD and less lumen reduction, compared with the BMS group （ P 〈 0.05 ）. Conclusions Oral administration of rapamycin demonstrates the same effect in the reduction of plaque burden and stent restenosis as the rapamycin during stent.