摘要目的探讨血管内皮生长因子(VEGF)基因心肌细胞转移促进异种生物瓣膜宿主内皮化的可行性.方法将经戊二醛及L-谷氨酸处理的牛心包置入猪的右心房,采用pcD2/hVEGF121基因缝线向右室心肌细胞转移VEGF基因(1 毫克).测定外周静脉及右心房血中VEGF蛋白含量,应用逆转录聚合酶链反应(RT-PCR)测定心肌组织中VEGF基因的表达,并取置入的牛心包进行组织学及超微形态学分析.结果转pcD2/hVEGF121基因10天后,VEGF基因组右心房血中VEGF蛋白含量明显高于空载质粒组(P<0.01).术后16天,VEGF基因组心肌VEGF mRNA表达产物明显高于空载质粒组及左心室对照组.此间,VEGF基因组牛心包宿主内皮覆盖率为空载质粒组的2.6倍(P<0.01).术后30天,VEGF基因组牛心包已完全内皮化,此外,该组心肌VEGF mRNA仍有较高的表达.结论采用基因缝线心肌细胞转移pcD2/hVEGF121基因,可以通过VEGF蛋白特异性地促内皮细胞生长,加速置入异种生物瓣膜宿主的内皮化.这为防止生物瓣膜钙化、改善生物瓣膜的生物相容性及长期耐久性提供了一种新途径.

abstractsObjective To investigate the feasibility of endothelialization of bioprosthesis by transfer of vascular endothelial growth factor (VEGF) gene.Methods Bovine pericardium treated with glutaraldehyde and L-glutamic acid was positioned into the pig right atrium. pcD2/hVEGF121 gene (1 mg) was transferred into the right ventricular myocardium using surgical sutures. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to evaluate the expression of myocardial VEGF mRNA. The determination of concentrations of VEGF protein in blood from both the right atrium and peripheral vein, and histological and ultrastructural analysis of implanted bovine pericardium were completed simultaneously.Results The concentration of VEGF derived from the right atrium in pcD2/hVEGF121 group was significantly higher than that in the pcD2 group 10 days after VEGF gene transfer (P<0.01). The expression of myocardial VEGF mRNA in pcD2/hVEGF121 group was much higher in comparison with that in the pcD2 group. The morphological analysis demonstrated that the coverage rate of host endothelium in the pcD2/hVEGF121 group was 2.6 times as fast as that in the pcD2 group at 16 days after VEGF121 gene transfer (P<0.01). Entire endothelialization occurred at 30 days after VEGF gene transfer. In addition, higher expression of myocardial VEGF mRNA was still available.Conclusions VEGF gene transfer by surgical suture can remarkably accelerate endothelialization of bioprosthesis, which may provide a new approach for inhibiting biological valve calcification and improve biocompatibility and long-term durability of the bioprosthesis.