[Study on inhibiting the intimal hyperplasia after rabbit artery injury by local transfection of tissue-type plasminogen activator gene].
OBJECTIVE
To observe the effects of local transfection of tissue-type plasminogen activator(tPA) gene on intimal hyperplasia of right external iliac artery in rabbits after operation injury, and its possible mechanism.


METHODS
Microsurgery injury was used to establish the intimal injury model of right external iliac artery in rabbits. 105 male New zealand rabbits were randomly divided into 3 groups (35 rabbits each group). Group A was normal saline control group, group B was pBudCE4.1-transfected group, and group C was pBudCE4.1/tPA-tansfected group. The normal saline, pBudCE4.1 and pBudCE4.1/tPA transfection solutions were injected into injured vessel walls. Each group was again divided into five subgroups (7 rabbits each subgroup) which were sacrificed at different time (2 d, 3 d, 7 d, 14 d and 28 d after operation). The injured vascular specimens were then harvested for pathologic examination, electron microscope observation, RT-PCR and immunohistochemical staining detection.


RESULTS
The intimal thickness and area of vessel walls in group C at every time points after operation were significantly less than those in group A and group B (P<0.01). The stenosis rate of vessels in group C at 28 days after operation decreased by 51.5% and 54.2%, respectively, as compared with groups A and B. The expression of tPA mRNA in group C was significantly higher than that in groups A and B at every time points after operation (P<0.01), reaching the peak at 7 days. The scanning electron microscope examination showed that there were a few thrombocytes adhering to vessel walls in group C but no thrombus, whereas a lot of thrombocytes and thrombi on vessel walls in groups A and B. Immunohistochemical staining exhibited that platelet-derived growth factor (PDGF)-positive cells in the vessels of group C were significantly more than those in group A and B (P<0.01).


CONCLUSIONS
Local transfection of tPA gene can inhibit hyperplasia of neo-intima and prevent restenosis, which is proof of concept for gene therapy of intimal hyperplasia.
Wu
Zhi-jie
ZJ
Department of General Surgery, First Affiliated Hospital, Zhejiang University, Hangzhou 310012, China. wzjxdfpxy@zju.edu.cn
Feng
Hu-yi
HY
Li
De-wei
DW
Shi
De
D
Zheng
Shu-sen
SS
D000818:Animals; D003251:Constriction, Pathologic / Q000235:genetics / Q000628:therapy; D015316:Genetic Therapy; D006965:Hyperplasia / Q000235:genetics / Q000628:therapy; D007083:Iliac Artery / Q000293:injuries* / Q000473:pathology* / Q000601:surgery / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D014162:Transfection; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology*
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator