转染PDGF-B mRNA的反义寡肽核酸抑制狗冠状动脉搭桥术吻合口再狭窄

目的探讨PDGF-B mRNA反义寡肽核酸对冠状动脉搭桥术吻合口再狭窄的影响。方法建立狗冠状动脉搭桥吻合口再狭窄模型;用合成的反义寡PNA以外科涤纶线携带并辅助治疗性超声波转导吻合口局部血管平滑肌细胞;分别用原位分子杂交和LSAB免疫组织化学法检测PDGF-B mRNA和PCNA表达;用形态测量法检测吻合口局部冠状动脉内膜厚度和面积。结果PNA显著抑制术后第4周吻合口局部冠状动脉内膜vSMCs表达PCNA和PDGF-B mRNA,与对照组相比抑制率分别为75.37%和71.64%;显著减少血管内膜厚度和面积。结论合成的反义寡PNA可部分抑制狗冠状动脉搭桥术吻合口再狭窄。

Transfection of an antisense oligo-peptide nucleic acid targeting against PDGF-BmRNA to inhibit the vascular anastomotic restenosis after coronary bypass

Objective] To elucidate the effect of antisense oligo-peptide nucleic acid(PNA) targeting against PDGF-BmRNA on vascular anastomotic restenosis after coronary bypass. Methods] A dog model of vascular anastomotic restenosis after coronary bypass was constructed and a synthesized PNA carried by surgery polyester suture was made to transfect the dog cardiomyocytes and vascular anastomotic vSMCs at the same time of the bypass, using a therapeutic ultrasound for the gene delivery. The proliferation of intimal vSMCs was observed by monitoring their expression of proliferating cell nuclear antigen(PCNA) and platelet-derived growth factor B chain mRNA(PDGF-B mRNA) with the LSAB and in situ hybridization, respectively. Coronary intimal thickness and area were measured. Results] This PNA could significantly inhibit the expressions of PCNA and PDGF-B mRNA by intimal vSMCs of coronary arteries 4 week after the bypass with the inhibitory rates of 75.37% and 75.64%, respectively and could reduce the intimal thickness and area. Conclusion] The designed PNA could inhibit vascular anastomotic restenosis after coronary bypass.