Pretreatment of isolated vein with rapamycin nanoparticles inhibits vein graft stenosis in rabbits

Abstract

To explore the effects of pretreatment of carbopol-encapsulated rapamycin-loaded nanoparticles (RPM-NP) on vein graft stenosis in a rabbit vein graft model. A segment of common carotid artery was replaced with a segment of external jugular vein in 40 rabbits. They were separated into four treatment groups, i.e. Group A: vein grafts were pretreated with intraluminal RPM-NP perfusion; Group B: peripheral venous veins were injected with RPM-NP; Group C: vein grafts received an equivalent perfusion of empty vehicle; Group D: vein grafts received no treatment. At Day 28 post-operation, the grafts and normal veins were harvested for histological examinations to analyze the indicators of intimal thickness, internal diameter, intimal/media thickness ratio and collagen volume index. At Day 28 post-operation, the intimal/media thickness ratios were 0.26 ± 0.02, 0.73 ± 0.05, 0.71 ± 0.04, 0.69 ± 0.03 and 0.24 ± 0.01 in Groups A, B, C and D and the normal vein; the collagen volume index 0.24 ± 0.03, 0.56 ± 0.06, 0.53 ± 0.07, 0.49 ± 0.08 and 0.21 ± 0.01 respectively. Compared with the normal veins, the pathological indicators of vein graft intimal thickness, internal diameter, intimal/media thickness ratio and collagen volume index had significant differences in Groups B, C and D (all P < 0.05). But there were no significant differences among 3 groups (all P > 0.05). Compared with the normal vein, the parameters of vein graft intimal thickness, internal diameter, intimal/media thickness ratio and collagen volume index had no significant difference in Group A (all P > 0.05). But as compared with other groups, these indicators had statistical significant difference in Group A (all P < 0.05). The local pretreatment of isolated vein with rapamycin nanoparticles may inhibit neointimal hyperplasia and prevent effectively vein graft stenosis.