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联合转染P~(21)基因和反义c-fos核酸对自体移植静脉中膜平滑肌细胞增生的影响

发布时间:2018-12-11 16:08
【摘要】:目的:本工作通过观察联合转染P~(21)基因和反义c-fos核酸对自体移植静脉的中膜平滑肌细胞(VSMC)增生的影响,探索一种理想的抑制自体移植血管再狭窄的基因疗法。 方法:选择健康雄性新西兰家兔20只,随机分成实验和对照组两组,每组各10只,所有动物均行自体右颈静脉和右颈总动脉移植手术。实验组移植静脉以腺病毒介导的P~(21)cDNA溶液浸泡和反义c-fos寡聚核苷酸凝胶涂布;对照组仅行空载腺病毒溶液浸泡和凝涂布。术后2周取出移植血管,分别对移植血管中膜平滑肌细胞进行计数和对移植血管中膜平滑肌细胞增殖细胞核抗原(PCNA)进行测定,测定PCNA阳性表达和VSMC的DNA含量及管腔狭窄度。 结果:实验组动物的VSMC增殖指数为12.74±1.78,对照组为26.25±5.75两组比较有极显著差异(P0.01);实验组PCNA阳性表达率为32.90±3.64,对照组为55.83±3.92两组比较有极显著差异(P0.01);实验组VSMC的DNA含量为5.79±1.59,对照组为11.62±2.19两组比较有极显著差异(P0.01);实验组管腔狭窄度为11.50±1.85,对照组为23.34±5.79两组比较有极显著差异(P0.01)。 结论:①联合转染P~(21)和反义c-fos可有效抑制自体移植静脉中膜平滑肌细胞的增生。②联合转染P~(21)和反义c-fos是一种有效的防治移植静脉发生再狭窄的基因疗法。
[Abstract]:Aim: to investigate the effect of combined transfection of P21 gene and antisense c-fos nucleic acid on the proliferation of (VSMC) in medial smooth muscle cells (MSMCs) after autologous vein transplantation, and to explore an ideal gene therapy for inhibiting restenosis of autologous grafts. Methods: twenty healthy male New Zealand rabbits were randomly divided into experimental group and control group with 10 rabbits in each group. Autogenous right jugular vein and right common carotid artery transplantation were performed in all the rabbits. The vein grafts in the experimental group were immersed in adenovirus-mediated P21 cDNA solution and coated with antisense c-fos oligonucleotide gel while those in the control group were only soaked in empty adenovirus solution and coated with coagulant. The vascular grafts were removed 2 weeks after operation. The number of MSMCs and the proliferating cell nuclear antigen (PCNA) were measured respectively. The positive expression of PCNA, the DNA content of VSMC and the degree of lumen stenosis were measured. Results: the proliferative index of VSMC was 12.74 卤1.78 in the experimental group and 26.25 卤5.75 in the control group (P0.01). The positive expression rate of PCNA was 32.90 卤3.64 in the experimental group and 55.83 卤3.92 in the control group (P0.01). The DNA content of VSMC was 5.79 卤1.59 in the experimental group and 11.62 卤2.19 in the control group (P0.01). The degree of lumen stenosis was 11.50 卤1.85 in the experimental group and 23.34 卤5.79 in the control group (P0.01). Conclusion: 1 Co-transfection of P21 and antisense c-fos can effectively inhibit proliferation of MSMCs in autogenous vein grafts. 2 Co-transfection of P21 and antisense c-fos is an effective method to prevent and treat vein graft reoccurrence. Narrow gene therapy
【学位授予单位】:青岛大学
【学位级别】:硕士
【学位授予年份】:2005
【分类号】:R363

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