黄连素对血管平滑肌细胞增殖、大鼠颈动脉球囊损伤模型及PTEN基因表达的影响

目的:探讨黄连素对血管平滑肌细胞(VSMC)增殖、大鼠颈动脉球囊损伤后动脉新生内膜形成及损伤后再狭窄的影响,及其影响是否通过改变PTEN(第10q23染色体的抑癌基因)的表达来实现。方法:MTT法检测黄连素对主动脉VSMC增殖的影响,实时定量RT-PCR及Western blot法测定黄连素对VSMC PTEN在转录及蛋白水平表达的影响。建立颈动脉球囊损伤模型,观察黄连素对新生内膜形成及再狭窄的影响及血管组织表达PTEN的变化。结果:黄连素抑制大鼠主动脉VSMC的增殖,改善损伤血管新生内膜形成及再狭窄;上调PTEN表达,且与浓度呈正相关,200μmol/L黄连素干预VSMC效果最佳;球囊损伤模型再狭窄的预防经过术前、术后各2周的黄连素处理,较单纯术后黄连素处理效果更佳。结论:黄连素可能通过上调PTEN表达来抑制VSMC增殖与球囊损伤模型内膜的增生及损伤后再狭窄。

Effects of berberine on the vascular smooth muscle cell proliferation,rat carotid artery balloon-injury model and PTEN expression

Objective:To evaluate the effects of berberine on the vascular smooth muscle cell(VSMC) proliferation and neointimal formation and restenosis in rat carotid artery balloon-injury model,and to explore whether the mechanisms were achieved by changing the expression of PTEN.Method:Application of MTT colorimetric assay to detect the effect of different concentrations of berberine on VSMC proliferation,real time RT-PCR and Western blot analyzed the effects of berberine on the mRNA and protein level of PTEN in VSMC.Rat carotid artery balloon-injury models were used to investigate the effect of berberine on neointimal formation,restenosis and the expression of PTEN.Result:Berberine inhibited rat aortic VSMC proliferation and improved neointimal formation and restenosis.Berberine up-regulated the expression of PTEN in a concentration-dependent manner,and optimal concentration of berberine was 200 μmol/L for VSMC.Berberine treatment of 14 days before the balloon injury and additional 14 days after the balloon injury was better than a simple post-operative 14 days management for the prevention of restenosis.Conclusion:Berberine inhibits VSMC proliferation and improves neointimal formation and restenosis after rat carotid artery balloon-injury model,probably through up-regulating the expression of PTEN.