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  • Title: [Study on inhibiting the intimal hyperplasia after rabbit artery injury by local transfection of tissue-type plasminogen activator gene].
    Author: Wu ZJ, Feng HY, Li DW, Shi D, Zheng SS.
    Journal: Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi; 2005 Mar; 21(2):213-7. PubMed ID: 15766409.
    Abstract:
    AIM: 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). CONCLUSION: 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.
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