核转录因子κB decoy寡核苷酸对移植静脉内膜增生的影响

The effect of nuclear transcription factor-κB decoy oligodeoxynucleotides on the intimal hyperplasia in vein graft

目的 研究核转录因子κB (NFκB)decoy寡核苷酸 (decoyODNs)对移植静脉内膜增生的抑制作用 ,探讨其作用机制。 方法 Wistar大鼠 72只 ,建立自体静脉移植模型 ,术后随机分为 :对照组 ,NFκBdecoyODNs 5 0 μg、2 0 0 μg组 ,杂码decoyODNs 5 0 μg、2 0 0 μg组 ,lipofectin +pluronic组等 6个组 ,施加不同的处理方法 ,在移植后 1、2周取材。组织形态学方法比较内膜增生程度 ,半定量RT PCR方法检测细胞间黏附分子 (ICAM) 1的mRNA表达 ,Westernblot和免疫组化方法检测p6 5、ICAM 1的蛋白产物表达。 结果 移植后 1、2周内膜增生明显 ,局部应用 5 0 μgNFκBdecoyODNs明显抑制内膜增生 ,抑制率为 2 2 %～ 31% ;2 0 0 μg组受抑制程度更为明显 ,抑制率达 4 1%～ 5 3% ,其他组内膜增生无明显变化。NFκBdecoyODNs能够抑制ICAM 1mRNA表达 ,p6 5和ICAM 1的蛋白表达均显著低于各对照组 ,抑制率为 30 %～ 5 7%。 结论 NFκBdecoyODNs可显著抑制移植静脉的内膜增生 ,其作用可能是通过减少黏附分子的基因转录及蛋白产物表达而实现的。

Objective To investigate the effect of nuclear transcription factor-κB decoy oligodeoxynucleotides(NFκB decoyODNs) on the intimal hyperplasia(IH) in vein graft in rats. Methods Autogenous vein graft model for 72 Wistar rats was established,and the interior jugular vein was transplanted to common jugular artery by microsurgical technique. The rats were divided into 6 groups according to different processing methods, including NFκB decoyODNs 50 μg and 200 μg, scramble decoyODNs 50 μg and 200 μg, control and lipofectin+ pluronic teams. Vein graft samples were harvested in 1 or 2 weeks after surgery and ICAM-1 mRNA were measured by RT-PCR. Western blotting and immunohistochemistry methods were also employed to detect the expression of p65 and ICAM-1. IH was compared at the same time. Results The intimal hyperplasia was evident in 1 or 2 weeks after vein graft, and ameliorated by 50 μg of NFκB decoyODNs with inhibition rate from 22% to 31%, 200 μg of NFκB decoyODNs had a higher inhibition rate from 41% to 53%. However, no effect was found in the other teams. The expression of ICAM-1 mRNA was also inhibited significantly by NFκB decoyODNs and more obvious in 2 weeks after surgery. Expression of ICAM-1 and p65 decreased greatly in NFκB decoyODNs team, which has a inhibition rate from 30% to 57%. Conclusion Transfection of NFκB decoyODNs can inhibit the IH after vein graft, which may be accomplished by the inhibition of gene expression of ICAM-1.