纤维蛋白胶外支架转染PCNA基因反义寡核苷酸预防移植静脉再狭窄

Effect of fibrin glue associated with antisense to PCNA on preventing restenosis of vein grafts

背景:前期研究成果,纤维蛋白胶不仅是一种良好的非限制性、生物可降解血管外支架,能够预防移植静脉内膜和中膜增生,而且是一种良好的药物缓释系统,能够提高血管外膜基因转染效率。目的:验证应用纤维蛋白胶外支架转染PCNA基因反义寡核苷酸预防移植静脉再狭窄的作用。方法:建立兔颈外静脉颈总动脉旁路移植模型,随机分为模型组、纤维蛋白胶支架组、纤维蛋白胶联合反义PNCA组。后两组分别给予纤维蛋白胶和纤维蛋白胶与携带PCNA反义寡核苷酸腺病毒的混合物于静脉桥外周均匀喷洒。结果与结论:移植后第28天模型组静脉移植物内膜和中膜增生明显,纤维蛋白胶外支架组静脉移植血管内膜和中膜增生程度明显减少(P<0.01),纤维蛋白胶联合反义PNCA组内膜和中膜增生程度明显少于纤维蛋白胶外支架组(P<0.05)。纤维蛋白胶联合反义PNCA组PCNA基因mRNA及蛋白表达明显减少纤维蛋白胶外支架组(P<0.05),纤维蛋白胶外支架组表达明显弱于模型组(P<0.05)。提示血管外膜反义PCNA转染可进一步抑制移植静脉管壁PCNA表达,纤维蛋白胶外支架联合反义PCNA对移植静脉内膜和中膜增生有协同抑制作用。

BACKGROUND：Preliminary findings show that fibrin glue is not only a good non-restrictive,extravascular biodegradable stent,but also can prevent intimal and medial hyperplasia of vein grafts.It is also a good drug delivery system that can improve the extravascular membrane gene transfection efficiency.OBJECTIVE：To verify the effect of fibrin glue associated with antisense to PCNA on preventing restenosis of vein grafts.METHODS：Rabbit models of external jugular vein carotid artery bypass grafting were prepared and then randomized into model group,fibrin glue group and fibrin glue＋antisense group.Commercially available fibrin glue and fibrin glue mixed with adenovirus expressing the antisense oligocleotides to PCNA were applied separately around vein grafts in the latter two groups,respectively.RESULTS AND CONCLUSION：Twenty-eight days after operation,the intimal and medial thickness and area was increased obviously in the model group and decreased significantly in the fibrin glue group（P 0.01）.A significant difference in the intimal and medial thickness and area was found between the fibrin glue group and fibrin glue＋antisense group（P 0.05）.The mRNA and protein expressions of PCNA in the fibrin glue＋antisense group was lower than those in the fibrin glue group（P 0.05）.The expression of PCNA in vein grafts can be inhibited by adventitial delivery of antisense to PCNA.The fibrin glue mixed with antisense has a synergistic effect on reducing the intimal and medial thickness and area of vein grafts.