[To study the effects of local co-transfection vascular endothelial growth factor165 and tissue-type plasminogen activator genes on inhibiting intimal hyperplasia after operation injury artery in rabbits].
OBJECTIVE
To observe the effects of local co-transfection vascular endothelial growth factor165 (VEGF165) and tissue-type plasminogen activator genes on inhibiting intimal hyperplasia and restenosis in rabbits artery after operation injury and possible mechanisms.


METHODS
Micrology operation injury was used to establish the model of intimal injury of right external iliac artery in rabbits. To select 120 male New Zealand rabbits and were randomly divided into 3 groups (n = 40, in each group): Group A (physiological brine control group), Group B (pBudCE4.1 group), Group C (pBudCE4.1/VEGF165-tPA group). The vas-wall of micrology operation injury were infused respectively physiological brine, pBudCE4.1 and pBudCE4.1/VEGF165-tPA transfection solution by micro-injector. Each group were divided into 5 subgroups (n = 8, in each subgroup) randomly according to the sacrifice times (2 d, 1 week, 2 week, 4 week and 8 week after operation). The injured vascular specimen were harvested for pathology test, electric microscopy study, reverse transcription-PCR examining and immunochemistry detecting.


RESULTS
The intimal area and narrow ratio of vases in Group C at every time point after operation were significantly lessened than that in Group A and Group B (P < 0.01). The narrow ratio of vases in Group C at 8 week after operation were decreased respectively by 57.9% and 59.0% than that in Group A and B. The expression of VEGF165 mRNA in Group C were increased significantly than that in Group A and B at every time point after operation (P < 0.01), the expression reached the peak at 1 week and continued to 4 week after operation. Immunohistochemical identified that tPA positive cell in Group C were significantly increased than that in Group A and B (P < 0.01) at every time point after operation.


CONCLUSIONS
Local co-transfection VEGF165 and tPA genes could restrain intimal hyperplasia and restenosis of vas, which lay a foundation for future multi-gene therapy of vascular intimal hyperplasia.
Wu
Zhong-jun
ZJ
Department of General Surgery, First Affiliated Hospital, Zhejiang University, Hangzhou 310012, China.
Yang
Su-fen
SF
Zheng
Shu-sen
SS
Shi
De
D
Li
De-wei
DW
Luo
Xu-dong
XD
D000818:Animals; D001158:Arteries / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology; D006965:Hyperplasia / Q000517:prevention & control; D066298:In Vitro Techniques; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010957:Plasmids; D011817:Rabbits; D011897:Random Allocation; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D017539:Tunica Intima / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D010959:Tissue Plasminogen Activator