| ackground and objectives: Saphenous vein graft occlusion is a main reason for the failure of coronary bypass grafting.Intimal smooth muscle cell (SMC)hyperplasis is a pivotal component of this pathobiology.Its exact etiology is unknown.lt is currently considered that many vasomotory material may take part in the occurrence and development of restenosis.Studies suggest c-myc is an immediate-early gene probed by many senators at present time.lt plays an crucial role in regulating cellular growth,proliferation,differentiation,and apoptosis.c-myc gene represents a common final pathway of platelet derived growth factor (PDGF),transforming growth factor (TGF),fibroblast growth factor(FGF).To date,it is a hot pot that the inhibition of VSMC proliferation using antisense digodeoxynucleotides(ODNs) prevent restenosis in cardiovascular system.However,previously much findings stemmed from arterial injury and in vitro;while it is relatively fewer regarding the issue on the c-myc expression of vein graft in vivo.Furthermore,currently,ballon or retroviral vector is often selected to act as gene transcathether deliver. These methods have many side effects.such as consuming time,costly expenditure,low efficiency and52002 *P8J眎fc:fc Bmtt?S#3fc c-mychigh toxicity etcl. In this study,antisense ODNs are carried out through soluble stents after vein grafting in a rabbit modeLOur purpose is to deeply elucidate the c-myc expression in vivo with different time;determine the relationship between c-myc and intimal hyperplasia (IH);evaluate whether IH can be inhibited through transcatheter delivery of c-myc ODNs with soluble stents.Subjects and methods: First,Twenty- five New Zealand rabbits were randomized into five groups(five in each).External jugular vein were interposed beween ipsilateral common carotid arteries.The vein grafts were harvested.at.6h,2days,lweek,2weeks,4weeks.after.grafting .Immunohistoche-mi cal labeling and morphologic analysis of vein graft sections were used to identify c-myc/alpha SMC actin positive cells.intimal and medial thickness of perfusion fixed vein grafts were measured with a computer digitized system. Second,After models were constructed ,sense,antisense,mismatch oligonucleotides were administered locally through soluble stents.Anmials were killed at 28 days and defined segments of vein grafts were sectioned and observed undered microscope.The intimal,medial thickness and ratios of intimal and medial thickness were measured with the aid of computer.Results:(l)50 randomized animals survived the experiment;no difference in animal survival or graft patency among the groups were observed.Intimal and medial thicking peaked at 1 week(71.07 ?4. 661 jam, 50. 77 ?3. 082um ,respectively)and were significantly thicker(analysis of variance p<0.01)than the same region at 6hr after graft implantation (5.81?.292um, 38.77?.278um respectively). While intimal and medial thickness at 2 weeks (74. 36 ?. 479um, 56. 99 ?. 418um Respectively) and 4 weeks (80.80 +2002 %-&3: ^tt:?#& c-myc2. 710um, 58. 06+4. 620um ,respectively) have no difference compared with 1 week.( analysis of variance p>0.05)(2)Staining for c-myc was also significantly higher (analysis of variance p<0.01)at Iweek (14.800+1.924 ) compared with that at 6hr (2.8 + 0.837 c-myc) .Subsequently,c-myc staining progressively decreased. (7. 8 ?0.837,4.2 +0.837), with a significant peak at lweek(analysis of variance p<0.01).It exactly coincides with the rapid phase of intimal hyperplasia. Results support there is a directed relationship between c-myc protooncogene expression and the proliferation state of the cells.(3)Twenty eight days after intervention ,the intimal thickness in c-myc antisense oligomers groups (43. 77 + 5. 891um) significantly decreased compared with control,stent,sense, mismatch groups (80.00 ?.335um, 76.06 +4.242um , 74.80 + 9.635um , 79.62 + 7.916um ,respectively,analysis of variance p<0.01 ) . While there was no difference among other four groups.The ratios of intimal to medial...
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