C型利钠肽在髂动脉球囊成形术后再狭窄发生中的作用

Effect of C-type natriuretic peptide on post-PTA restenosis in iliac artery of atherosclerotic rabbit model

目的:探讨C型利钠肽(C-type natriuretic peptide,CNP)在髂动脉球囊成形术后再狭窄发生中的作用。方法:构建兔髂动脉粥样硬化模型,将动物分为球囊成形术(Percutaneous transluminal angioplasty,PTA)组和假手术组,观察PTA术后CNP表达变化;将CNP基因转染髂动脉,观察CNP基因过表达对PTA术后再狭窄的影响。结果:PTA术后2、4周RT-PCR、荧光定量RT-PCR、免疫组化、Western blot检测显示CNP表达明显降低;PTA术后8周CNP表达无明显差异。CNP基因过表达组内膜增生程度、内膜/中膜比及血管狭窄率明显降低。结论:CNP表达减少可能是PTA术后再狭窄发生原因之一,增加CNP表达可一定程度预防再狭窄发生。

Objective：To discuss the potential role of C-type natriuretic peptide（CNP） on occurrence of vascular restenosis after percutaneous transluminal angioplasty（PTA）.Methods：CNP expression was detected with RT-PCR,real-time quantitative RT-PCR,Western blot and immunohistochemistry after PTA in iliac artery in rabbit model of atherosclerosis.Reconstructed plasmid pcDNA3.1（＋）/hCNP was transfected with polyethylenimine in iliac artery to investigate the effect of CNP over-expression on post-PTA restenosis.Results：CNP expression decreased markedly 2 and 4 weeks after PTA.The relative levels of CNP mRNA expression revealed with RT-PCR were 0.38±0.06 vs 0.98±0.15 and 0.43±0.05 vs 1.01±0.12（P〈0.001）.With real-time quantitative RT-PCR,Ct value ratios were 2.06±0.17 vs 1.27±0.10 and 2.10±0.11 vs 1.23±0.10（P〈0.001）.The relative levels of CNP protein expression detected with Western blot were 0.15±0.03 vs 0.31±0.06 and 0.13±0.04 vs 0.30±0.05（P〈0.001）.A lighter dyeing was identified in PTA group in both 2 weeks and 4 weeks with immunohistochemistry.CNP mRNA and protein expressions were not different on 8-week spot between PTA and non-PTA groups.Hyperplasia and restenosis rate after PTA declined significantly in CNP over-expression group compared with non-transfected one（0.29±0.07 vs 0.76±0.06;0.31±0.02 vs 0.57±0.05,P〈0.001）.Conclusion：CNP down-expression may be one of the reasons to induce post-PTA restenosis.CNP gene transfection is potential to prevent vascular restenosis.