Effect Of BFGF Antisense Oligonucleotides On Intimal Hyperplasia Of Vein Autografts Of Rats

Objective: Autogenous vein grafts are the key treatmental methods of vascular occlusion diseases. Recent years, with maturing of treatment strategy and rapid growth of technologies, the early outcome has been advancing significantly. But intimal hyperplasia (IH) accounts for 20% to 40% of restenosis, which seriously hampers long-term outcome. Therefore it is imperative to elucidate the pathogenesis of restenosis and to develop new strategy for the precaution and treatment of restenosis. The cellular and molecular mechanism that lead to the restenosis have not been clearly defined. Abundant evidence is available to support roles for growth factors as key signal molecules in the vascular smooth muscle cells proliferation and IH. Many features of lesions can be readily explained by known properties of growth factors. Among the growth factors, it is remarkable that bFGF as a potent mitogen and chemotaxis together with its ability to transform cells is a leading candidate to play a major role in restenosis. Our purposes of the study are to observe the effect of bFGF antisense oligonucleotides on IH of vein autografts of rats and to discuss the pathogenesis that antisense oligonucleotides prevent restenosis after autogenous vein grafting by the antisense nucleic acid techniques. The results of our study will provide theoretical base for the more efficient biotherapy of restenosis.Methods: 48 Wistar rats were selected and were divided randomly into AODN (antisense oligodeoxynucleotide), SODN (sense oligodeoxynucleotide), RODN (random oligodeoxynucleotide), and control groups. The animal model of autogenous vein graft was established through transplanting the left commonjugular veins into abdominal aortas. The transplanted veins of experimental groups were coated with antisense oligonucleotide polymer gel (Pluronic F127) just after anastomosis, while control groups were nothing to be coated. Vein grafts were harvested at 1 week, 2 weeks after operation respectively. Specimens were fixed with formalin and embedded in paraffin, then processed with hematoxylin-eosin stains. The mean intimal thickness(IT) and intimal / medial(I/M) thickness ratios were measured by computer graph analysis system. Grafts were immunohistochemically stained to assess bFGF protein production, and then percentages of positive cell were calculated. Groups were compared with analysis of variance by SPSS 11.5 software.Results: The animal model of autogenous vein graft was successfully established. At 1 week after operation, the intimae of vein grafts in SODN, RODN and control groups thickened slightly, while in AODN group didn't thicken obviously. The IT and I/M thickness ratios of AODN group were limited as compared with the other groups (P<0.05), while there was no significant difference in SODN, RODN and control groups (P>0.05). At 2 weeks, the intimae of vein grafts in SODN, RODN and control groups were thicker significantly as compared with those at 1 week (P<0.05). The IT and I/M thickness ratios of AODN group were lower than the other groups (P<0.05), while there was no significant difference in SODN, RODN and control groups (P>0.05). At 1 week after operation, bFGF positive cell percentages of AODN group were lower than other groups by immunohistochemical stain (PO.05), while there was no significant difference in SODN, RODN and control groups (P>0.05). At 2 weeks, bFGF positive cell percentages of SODN, RODN and control groups were greater than those at 1 week (P<0.05). bFGF positive cell percentages of AODN group were lower than other groups (PO.05), but there was no significant difference in...