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联合转染反义PDGF寡核苷酸和tPA基因抑制血管内膜增生的实验研究 被引量:1

Effects of platelet derived growth factor antisense oligodeoxynucleotides and tissue-type plasminogen activator gene transfection on inhibition of intimal proliferation
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摘要 目的:观察血管局部联合转染血小板源性生长因子(PDGF)反义寡核苷酸(AODN)和组织型纤溶酶原激活物(tPA)基因对自体移植动脉内膜增生的影响,并探讨其可能机制。方法:选100只新西兰雄性白兔,随机分为4组(每组25只):A组(对照组)、B组(PDGF-AODN转染组)、C组(tPA基因转染组)、D组(PDGF-AODN和tPA基因联合转染组)。将同一只兔的左、右髂外动脉(各1.0cm)对换移植,移植血管分别用PDGF-AODN和pBudCE4.1/tPA液浸泡,血管吻合口用上述液体浸泡过的缝线吻合。每组按实验终点(术后3d、1w、2w、4w和8w)分为5个亚组,术后各实验终点取移植血管标本,用于病理学检测、电镜观察、发色底物检测tPA活性实验3、H-TdR掺入实验和免疫组织化学染色检测。结果:术后各时间点D组移植血管的内膜面积、管腔狭窄程度、3H-TdR掺入量和PDGF阳性细胞数均显著低于A组(P<0.01),而且亦明显低于B和C组(P<0.05)。扫描电镜观察显示C组和D组血管壁只见少量血小板附着,未见血栓形成,而A组和B组血管壁可见大量血小板附着,且有血栓形成。术后3d、1w、2w、4w时C组与D组的tPA基因表达产物活性明显高于A组(P<0.01)。结论:血管局部联合转染PDGF-AODN和tPA基因能有效抑制VSMC增殖,阻止内膜增生,防止移植血管狭窄。 Objective: To observe the effects of co-transfection of platelet derived growth factor antisense oligodeoxynucleotides (PDGF-AODN) and tissue-type plasminogen activator (tPA) gene on inhibition of intimal proliferation of auto-transplantion artery, Methods : One hundred male New Zealand rabbits were randomly divided into four groups (25 in each),,Group A (control group),Group B (PDC-F-AODN transfection group),Group C (tPA gene transfection group) and Group D(PDGF-AODN and tPA co-transfection group). The left and right external iliac arteries were transplanted reciprocally. The transplanted arteries were respectively soaked in PDGFAODN, pBudCE4. 1/tPA and PDGF-AODN plus pBudCE4. 1/tPA solution about 15 minute before transplantation, The rabbits were sacrificed at 3d, 1w, 2w, 4w and 8w after operation. The specimens were harvested for pathologic examination,electron microscopy,chromogenic substrate test,^3H-TdR incorporation test and immunohistochemical staining, Results: The scan electron microscopy showed that there were a few thrombocytes on vas-wall of Group C and D without thrombus,whereas there were abundant thrombocytes and thrombus forming on vas-wall of Group A and B, The intimal area,stenosis ratio of transplanted artery,^3H-TdR incorporation,the number of PDGF positive cell in Group D were significantly less than those in Group A (P〈0.01) ,Group B and Group C (both P〈0.05). The activity of tPA gene products in transplanted vas-wall of Group D was significantly higher than that of Group A (P〈0.01). Conclusion.. Local co-transfection of PDGF-AODN and tPA gene can effectively inhibit the proliferation of vascular smooth muscle cells,hyperplasia of intima and restenosis of transplanted artery.
出处 《浙江大学学报(医学版)》 CAS CSCD 2005年第4期320-325,338,共7页 Journal of Zhejiang University(Medical Sciences)
基金 国家重点基础研究发展规划(973)基金资助项目(2003CB515501) 国家自然科学基金资助项目(30270514)
关键词 寡核苷酸类 反义/分析 血小板源生长因子/分析 组织型纤溶酶原激活物 基因表达 Oligonucleotides,antisense/analysis Platelet-derived growth factor/analysis Tissue plasminogen activator Gene expression
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