转导C型钠尿肽基因对血管成形术后血管平滑肌细胞增殖的影响
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广东省医学科研基金(A2003056)


Effects of C-type Natriuretic Peptide Gene Transduction on Vascular Smooth Muscle Cell Proliferation after Angioplasty
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    摘要:

    目的观察局部转导C型钠尿肽基因对损伤后血管平滑肌细胞增殖的影响。方法将84只雄性新西兰大白兔随机均分为正常、对照和实验3组。后2组高脂饮食喂养,并以球囊损伤兔髂动脉建立再狭窄模型。对照组局部转导逆转录病毒载体携带的碱性磷酸酶基因;实验组局部转导逆转录病毒载体携带的C型钠尿肽基因。于术后第3天、第1周末、第2周末和第4周末取损伤段动脉进行氚标胸腺嘧啶脱氧核苷掺入实验和增殖细胞核抗原免疫组织化学检测,采用计算机图像分析仪测量血管腔面积、内膜厚度、内膜面积、内膜与中膜面积比。结果对照组和实验组在后3天血管内膜面积、内膜厚度、内膜/中膜比值开始逐渐增加,术后2周上述各值显著增加,但实验组上述指标明显低于对照组(后第3天、第1周时p<0.05,后第2周、第4周时p<0.01)。氚标胸腺嘧啶脱氧核苷掺入实验发现,术后第3天,对照组和实验组氚标胸腺嘧啶脱氧核苷掺入量开始增加,但两组无显著差异(p<0.05);术后第1周,实验组氚标胸腺嘧啶脱氧核苷掺入量明显低于对照组(p<0.05),术后4周时,实验组氚标胸腺嘧啶脱氧核苷掺入量已降至接近正常水平(p<0.05),而对照组氚标胸腺嘧啶脱氧核苷掺入量增加值仍高于正常组(p<0.01)。增殖细胞核抗原免疫组织化学显示对照组髂动脉损伤后2周在内膜层可见大量增殖细胞核抗原阳性细胞,而实验组增殖细胞核抗原阳性细胞表达不显著。结论局部转染C型钠尿肽基因可有效抑制血管成形术后血管平滑肌细胞增殖及内膜增生。

    Abstract:

    Aim To investigate the effects of C-type natriuretic peptide (CNP) gene transduction on vascular smooth muscle cell proliferation after angioplasty. Methods Eighty-four rabbits were divided into 3 groups equally:normal,control and test group. The control and test group had been given high-cholesterol diet from 7 d pre-experiment to being killed. All rabbits were fed by high-cholesterol diet. Restenosis models were established by injured iliac artery in control group and test group. In control group, alkaline phosphatase gene that retroviral vector carried was transferred at injured site. In test group,CNP gene that retroviral vector carried was transferred at injured site. Iliac arteries injured were harvested for ~3H-TdR incorporation, immunohistochemistry analysis of proliferating cell nuclear antigen (PCNA). Lumen area, neointimal thickness, neointimal area, neointimal area/media area were measured by image analysing system. Results Iliac arteries injured by balloon, 3 days later, neointimal thickness, neointimal area and neointimal area/media area were increased in control group and test group, and the index was markedly increased after 2 weeks later. The index of test group was less than control group (p<0.05 or p<0.01). Incorporation of ~3 H-TdR became higher 3 days later after balloon angioplasty in control group and test group, but there was no significant difference in two groups (p<0.05). ~3H-TdR incorporation of test group was less than control group 1 week later after balloon angioplasty (p<0.05). ~3H-TdR incorporation of test group was near to normal level 4 weeks later after balloon angioplasty (p<0.05), but there was still higher in control group (p<0.01). Immunohistochemistry staining of PCNA suggested that large numbers of PCNA-positive cells were seen at intima layer 2 weeks later after balloon angioplasty in control group, but there were no conspicuous express in test group. Conclusion Local CNP gene transduction could effectively inhibit vascular smooth muscle cell (VSMC) proliferation and intimal hyperplasia after angioplasty.

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裴晓阳,冯建章,徐亚伟,朱梦云,于学靖.转导C型钠尿肽基因对血管成形术后血管平滑肌细胞增殖的影响[J].中国动脉硬化杂志,2006,14(3):201~204.

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  • 收稿日期:2005-01-27
  • 最后修改日期:2006-02-14
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