静电纺丝血管外支架抑制静脉移植物内膜增生

A novel external stent prepared by electospinning reduces neointimal hyperplasia of vein grafts

目的探讨聚-3-羟基丁酸与聚-4-羟基丁酸聚酯[P（3HB—co-4HB）]静电纺丝血管外支架预防静脉移植物内膜增生的机制。方法静电纺丝技术制备P（3HB—co-4HB）血管外支架。SD大鼠随机分成2组，每组24只，建立颈外静脉-颈总动脉血管移植模型：无支架（NS）组和非限制支架（Ps）组。分别于术后3、7、14、28d取静脉移植物标本，计算机图像系统分析内膜、中膜厚度和面积，免疫组织化学检测静脉移植物增殖细胞核抗原（PCNA）表达。逆转录．聚合酶链反应（RT-PCR）检测静脉移植物血小板源性生长因子-BB（PDGF—BB）和组织因子（TF）mRNA表达。结果术后7、14、28d支架组静脉移植物内膜与中膜的厚度和面积明显低于无支架组（P〈0．05）。两组PCNA表达均增加并在术后14d最高，而支架组在术后7、14dPCNA表达低于无支架组（P〈0．05）。术后3、7d支架组PDGF—BB和TFmRNA表达明显低于无支架组（P〈0．01）。结论静电纺丝P（3HB—co-4HB）血管外非限制性支架能抑制静脉移植物内膜增生，并通过降低静脉移植物管壁早期组织因子表达发挥作用。

Objective To investigate the effect of a novel stent based on P（3HB-co-4HB） on neointimal thickening in the rat vein graft （VG） and its possible mechanism. Methods External stents of P （3HB-co-4HB） were prepared by electospinning. Carotid interposition bypass grafting was performed with the jugular vein in Sprague-Dawley rats. After engraftment, external stents with 1.8 mm were placed in 24 rats. Forty-eight modeled rats were equally divided into two groups ：non-stent control （NS）, 1.8 mm external stent （PS）. The VGs were harvested at the 3rd, 7th, 14th, 28th d after operation, respectively. The thickness, area of neointima, and media of the VG were calculated by computer imaging analysis system. The expression of proliferating cell nuclear antigen （PCNA） was detected by using immunochemistry. RT-PCR was used to assay the expression of PDGF-BB and tissue factor mRNA. Results The thickness, area of both neointima,and media of the VG in PS group were increased mildly at the 7th, 14th, and 28th d re- spectively, which was significantly less than NS group （ P 〈 0.05 ）. The number of PCNA positive cells was increased in two groups and reached the peak at the 14th day postoperatively. The expression of PCNA in PS group was decreased significantly in comparison with NS group at the 7th, and 14th day （ P 〈 0.05 ）. The expression of PDGF-BB and TF mRNA in PS group was significantly less than that in NS group at the 3rd,7th day after operation （P 〈 0.01 ）. Conclusion A novel external stent based on P （3HB-co-4HB） can reduce early intimal and medial hyperplasia, possibly through the downregulation of TF expression in early experimental vein grafts.