低分子肝素纳米粒子抑制兔血管平滑肌细胞增殖

Low molecular weight heparin nanoparticles inhibit proliferation of vascular smooth muscle cell in rabbits

目的探讨低分子肝素(LMWH)纳米粒子抑制血管平滑肌细胞(VSMC)增殖的作用及可能的作用机制。方法建立32只兔颈内静脉-颈动脉移植模型,并随机分为生理盐水灌注组(A)、LMWH灌注组(B)、生理盐水灌注+术后皮下注射LMWH组(C)、LMWH纳米粒子灌注组(D),每组8只。术后4周末截取移植静脉,行免疫组化检测增殖细胞核抗原(PCNA)蛋白的表达;并行RT-PCR检测移植血管单核细胞趋化蛋白-1(MCP-1)、碱性成纤维细胞生长因子(bFGF)、血小板源性生长因子(PDGF)基因mRNA的表达。结果与A、B、C三组相比,D组的PCNA阳性细胞指数明显降低(P<0.05),其MCP-1、bFGF、PDGF基因mRNA的表达水平也低于另外三组(P<0.05)。结论LMWH纳米粒子通过抑制平滑肌细胞的增殖与迁移而抑制了血管移植后内膜增生。其作用机制可能是通过降低MCP-1、bFGF、PDGF基因mRNA的表达而实现的。

Objective To study the inhibitory effect and possible mechanism of low molecular weight heparin（LMWH） nanoparticles on the proliferation of vascular smooth muscle cell（VSMC）.Methods After establishment of jugular vein to common carotid artery bypass grafting model,32 rabbits were randomly divided into 4 groups of A perfused with normal saline,B perfused with LMWH,C perfused with normal saline plus LMWH hypodermic injection after surgery,and D perfused with LMWH nanoparticles with 8 rabbits each.Four weeks after surgery,the grafts were harvested for PCNA immunohistochemistry analysis and the expressions of monocyte chemoattractant protein-1（MCP-1）,basic fibroblast growth factor（bFGF）,and platelet-derived growth factor（PDGF） were detected by RT-PCR.Results PCNA staining positive cells were less in group D than those in other three groups（P0.05）.The expressions of mRNA of MCP-1,bFGF,PDGF was lower in group D than those in other three groups as well（P0.05）.Conclusion LMWH nanoparticles inhibit the intimal hyperplasia of the graft by prohibiting VSMC proliferation and migration.The possible mechanism might be related to the decreases in the expressions of MCP-1,bFGF and PDGF mRNA.