雷帕霉素纳米粒局部处理兔离体静脉对防治其移植后狭窄的作用

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

目的 研究用纳米缓释技术处理的雷帕霉素（RPM-NP）对移植静脉狭窄的防治作用.方法 选取家兔40只,建立兔颈外静脉间位移植至颈总动脉的移植静脉模型,按处理方式不同,分为4组：药物纳米局部干预组（RPM-NP局部处理颈外静脉,n=10,A组）、药物纳米全身干预组（RPMNP周围静脉滴注,n=10,B组）、空白纳米局部干预组（空白纳米粒局部处理颈外静脉,n=10,C组）和未干预组（不做上述处理,n=10,D组）.术后28 d,切取各组移植静脉和对侧正常静脉,病理学检测移植静脉内膜厚度、内径、内膜/中膜厚度比以及胶原容积指数.结果 移植静脉的组织病理学检测结果表明,A、B、C、D组移植静脉和对侧正常静脉的内膜/中膜厚度比分别为0.26±0.02、0.73±0.05、0.71 ±0.04、0.69±0.03、0.24±0.01,胶原容积指数比分别为0.24±0.03、0.56±0.06、0.53±0.07、0.49±0.08、0.21 ±0.01.B、C、D组的组织病理学（移植静脉内膜厚度、内径、内膜/中膜厚度比以及胶原容积指数）与对侧正常静脉组比较,均出现明显的病理学改变,差异均有统计学意义（均P＜0.05）；3组之间移植静脉的组织病理学结果比较,差异均无统计学意义（均P＞0.05）.而A组移植静脉的组织病理学结果与对侧正常静脉比较,差异无统计学意义（P＞0.05）；与其他3组比较,差异有统计学意义（P＜0.05）.结论 采用纳米缓释技术处理的雷帕霉素,对离体的移植静脉行管腔内局部处理,能抑制移植静脉内膜增生,防治移植静脉狭窄.

Objective To explore the effects of pretreatment of carbopol-encapsulated rapamycinloaded nanoparticles（RPM-NP）on vein graft stenosis in a rabbit vein graft model.Methods 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 postoperation,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.Results 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）.Conclusion The local pretreatment of isolated vein with rapamycin nanoparticles may inhibit neointimal hyperplasia and prevent effectively vein graft stenosis.