Experimental Research On The Prevention Of Autologous Vein Graft Restenosis By Fibrin Glue Associated With TIMP-1Adventitial Gene Transfer To Vein Grafts

Objective:To investigate the mechanism of attenuation of vein graft restenosis by applying fibrin glueassociated with tissue inhibitor of metalloproteinase-1(TIMP-1)locally on vein graft and offer anew idea for clinical prevention of vein graft restenosis.Method:1. Animal model: Thirty New Zealand white rabbits were randomly divided into3groups with10rabbits in each group: non-support group(NS group), fibrin gluegroup(FS group) and fibrin glue+TIMP-1group(TS/FS group).All animalsunderwent unilateral jugular vein into common carotid artery interposition grafting.NS group:the vein grafts were accepted no any management;FS group:0.8ml fibringlue was locally applied on the adventitia of the vein grafts as external support;TS/FSgroup:0.8ml fibrin glue mixing with adenoviurs expressing TIMP-1was locallyapplied on the adventitia of the vein grafts.2. Specimens detection and Result analysis:After operation, vein grafts wereharvested at28days for histopathology measurement of intimal thickness, mediathickness and intimal areas,media areas,RT-PCR and Western-blot analyses ofTIMP-1gene expression of each group vein grafts.Results:1. Animal model was established successfully:28days after the operation, themean intimal thickness,intimal areas of the TS/FS group were(37.94±3.72)μm and(0.555±0.048)mm~2respectively, which were reduced obviously comparing with NSgroup and FS group (P＜0.01).The mean media thickness,media areas of the TS/FSgroup were(28.66±2.71)μm and(0.462±0.048)mm~2respectively, which weredecreased statistically comparing with NS group and FS group (P＜0.01).2.28days after the operation, RT-PCR and Western-blot analysis showed thatthe gene expression of TIMP-1was increased in TS/FS group compared with NSgroup and FS group (P＜0.05). Conclution:1. The expression of TIMP-1in vein grafts can be overexpression by fibrin glueassociated with adventitial delivery of TIMP-1.2. The fibrin glue mixing with TIMP-1has synergistic effect on reducingneointimal and media thickness of vein grafts.