不同浓度的纤维蛋白原对移植静脉内膜增生的作用

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（intimal hyperplasia,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(human saphenous vein,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0.544。（2）FG浓度在5.0mg/ml时：其内膜与中膜厚度比为0.421；内膜与中膜面积比为0.382;5′－BrdU阳性细胞比为0.501。（3）二者与对照组（不含FG）的内膜与中膜厚度比0.215；内膜与中膜面积比0.229；5′－BrdU阳性细胞比0.363，比较差异均在显著性（P＜0.05）。2.5mg/ml和5.0mg/ml两组之间相比差异无显著性（P＞0.05）。（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9P＞0.05）。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 治疗对再狭窄可能有一定的防治作用。

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

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.