不同浓度的纤维蛋白原对移植静脉内膜增生的作用

The Effect of Fibrinogen on Intimal Hyperplasia in Organ Culture of Human Saphenous Vein

目的 :研究不同浓度的纤维蛋白原 (fibrinogen ,FG )对移植静脉内膜增生 (intimalhyperplasia ,IH )的作用。方法 :建立移植静脉IH模型 ,在 9例血管移植术中取正常人大隐静脉 (humansaphenousvein ,HSV )行体外培养 ,培养液中施加不同浓度的FG。培养 14d后 ,应用组织学、5′ BrdU免疫组化染色 ,计算机图像分析 ,测量内膜与中膜厚度、面积比 ,计数 5′ BrdU阳性细胞比 ,观察不同浓度的FG对IH的影响。结果 :(1)FG浓度在 2 .5mg/ml时 :培养静脉片的内膜与中膜厚度比为 0 .387;内膜与中膜面积比为 0 .396 ;5′ BrdU阳性细胞比为 0 .5 44。 (2 )FG浓度在 5 .0mg/ml时 :其内膜与中膜厚度比为 0 .42 1;内膜与中膜面积比为 0 .382 ;5′ BrdU阳性细胞比为 0 .5 0 1。 (3)二者与对照组 (不含FG )的内膜与中膜厚度比 0 .2 15 ;内膜与中膜面积比 0 .2 2 9;5′ BrdU阳性细胞比 0 .36 3 ,比较差异均有显著性 (P <0 .0 5 )。 2 .5mg/ml和 5 .0mg/ml两组之间相比差异无显著性 (P >0 .0 5 )。 (4 )FG浓度在 0 .5mg/ml时 ,上述项检测指标与对照组相比 ,差异无显著性 (P >0 .0 5 )。结论 :高浓度的FG对IH有直接促进作用 ,提示血管移植术后局部高浓度FG可导致再狭窄和闭塞 ;低浓度的FG对IH无明显影响 ,提示临床上降纤治疗对?

Objective:The aim of this study was to identify fibrinogen ( FG ) on the development of intimal hyperplasia ( IH ), using an organ culture model. Methods:Segments(n=9 ) of human saphenous vein ( HSV ) wereharvested during coronary artery or infrainguinal vein bypass surgery. The culture medium supplemented with FG (from0 mg/ml to 5 mg/ml ). The proliferation of smooth muscle cell ( SMC ) quantified by 5′ Bromodeoxyuridine (5′ BrdU) uptake in the final four days of the culture period. Histologic analysis and computerized morphometric analysis were used to determine intimal and medial thickness and area,then the intima/media thickness ratio and intima/media area ratio were calculated. Monoclonal antibodies to 5′ BrdU were used as an immunohistochemical maker for proliferating SMC. Results:Addition of FG ( 2.5 mg/ml ) to the cultured medium caused a significant increase in median ( range ) of intima/media thickness ratio and intima/media area ratio of these segments when compared with the normal cultured vein segments ( Wilcoxon paired rank test ):0.387versus 0.215(P=0.017 )and 0.396 versus 0.229(P=0.015 ),respectively. Addition of FG ( 5.0 mg/ml ) to the cultured medium also caused a significant increase in median ( range ) of intima/media thickness ratio and intima/media area ratio of these segments when compared with the normal cultured vein segments: 0.421 versus 0.215(P=0.008 )and 0.382 versus 0.229 (P=0.011 ),respectively. However,there were no significant differences in the two vein segments which 2.5 mg/ml or 5.0 mg/ml FG in cultured medium (P>0.05 ).In addition, there was no significant difference in the median ( range ) of intima/media thickness ratio and intima/media area ratio of the segments which FG ( 0.5 mg/ml ) in cultured medium when compared with the normal cultured vein segments ( P>0.05 ). These were supported by SMC proliferation index using staining with 5′ BrdU. Conclusion:High concentration FG at local preianastimotic area may an important factor for IH and early postoprative vein graft restenosis or occlusion.