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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 investigate the effects of low molecular weight heparin (LMWH) nanoparticles on the proliferation of vascular smooth muscle cells (VSMC) and its possible mechanism. Methods Thirty-two rabbit models of internal carotid artery-carotid artery graft were established and randomly divided into normal saline group (A), LMWH group (B), normal saline group and subcutaneous injection of LMWH group (C) Group (D), 8 rats in each group. At the end of the fourth week after transplantation, the grafted veins were taken and the expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. The expression of MCP-1 and bFGF Factor (bFGF), platelet-derived growth factor (PDGF) gene mRNA expression. Results The index of PCNA positive cells in group D was significantly lower than that in group A, B and C (P <0.05), and the mRNA expression of MCP-1, bFGF and PDGF in group D was lower than that in the other three groups ). Conclusion LMWH nanoparticles inhibit intimal hyperplasia after vascular graft by inhibiting the proliferation and migration of smooth muscle cells. Its mechanism may be through reducing MCP-1, bFGF, PDGF gene mRNA expression achieved.