超声微泡介导雷帕霉素抗兔腹主动脉球囊损伤术后再狭窄

Inhibition of abdominal aorta restenosis after aorta balloon injury induced by rapamycin mediated by ultrasound-targeted microbubbles destruction in rabbits

目的探讨利用超声靶向破坏微泡(UTMD)介导雷帕霉素(RPM)对兔腹主动脉球囊损伤术后新生内膜的作用及对p27、血管内皮生长因子(VEGF)表达的影响。方法选取48只兔建立腹主动脉球囊损伤模型,术后3天分为6组(每组8只):A组,空白对照组;B组,超声+微泡组;C组,RPM组;D组:超声+RPM组;E组,UTMD+高剂量RPM组;F组,UTMD+低剂量RPM组。术前及术后28天分别进行超声检查,检测内-中膜厚度(IMT)。术后第28天病理检测内/中膜厚度比值(I/M)及p27、VEGF表达情况。结果术后第28天超声显示A、B、C、D组IMT较E、F组明显增加(P均<0.01),CD-FI可见充盈缺损。病理检测显示E、F组I/M减低,p27表达增高、VEGF表达降低,与其余组比较差异均有统计学意义(P均<0.01)。结论 UTMD介导RPM可抑制兔腹主动脉球囊损伤术后新生内膜增生及增高p27、降低VEGF表达。

Objective To explore the inhibition effect on neointima formation and restenosis in rabbit aorta balloon injury model by using rapamycin mediated by ultrasound-targeted microbubbles destruction （UTMD）. Methods Balloon injury was performed in aorta to induce neointima formation in 48 rabbits. The rabbit models were randomly divided into 6 groups （each n=8） 3 days after operation： Group A, control group; group B, ultrasound-k-microbubble; group C, rapamyein; group D, ultrasound＋rapamycin; group E, UTMDq-high dose rapamycin; group F, UTMD-I-low dose rapamycin. Ultra- sonography was performed to detect the intima-media thickness （IMT） before the surgery and on the 28th day after the sur- gery. On the 28th day after surgery, the aortas were taken to detect the intima thickness/media thickness （I/M） , and the expression of p27 and VEGF were detected using pathological means. Results On the 28th day, ultrasonography showed that the IMT was higher in group A, B, C and D than that in group E and F （all P〈0. 01）. Filling defect was observed in group A, B, C and D. Pathological results displayed that I/M was lower in group E and F. The level of p27 expression in group E and F were higher than that of group A, B, C and D （all P〈0.01）. The level of VEGF expression in group E and F were lower than that of group A, B, C and D （all P〈0.01）. Conclusion UTMD mediated rapamycin therapy can inhibit the neointima formation in rabbits aorta after balloon injury.