【摘要】 背景醛糖还原酶增强氧化应激,促进细胞分裂增殖,激活转录因子、核因子кB(NF-кB),但在血管再狭窄中起的作用报告不多。目的研究醛糖还原酶(AR)在大鼠再狭窄血管中的表达,探讨AR表达与内膜增生的关系,AR拮抗剂依帕司他对再狭窄血管中AR的表达及AR的抑制作用。方法健康雄性SD大鼠24只,随机分成对照组(A组)、手术未干预组(B组)及手术+依帕司他组(C组),每组8只。用通气-干燥法损伤B组及C组大鼠右侧颈总动脉,左侧颈总动脉作为对照。分别于7d及14d后处死大鼠,HE染色以观察内膜及中膜增生情况,并计算内膜、中膜面积及其比值,FISH原位杂交及免疫组化检测AR及NF-кB的表达。结果1)术后第7天损伤侧血管内膜增生明显,第14天后内膜增生进一步加重,对照血管无明显增生。2)依帕司他明显抑制血管内皮损伤后血管内膜增生、血管内膜面积、血管内膜与中膜面积比值明显低于未干预组(P<0.05或P<0.01)。3)AR及NF-кB在损伤侧血管中的表达明显强于对侧。依帕司他明显抑制AR及NF-кB的表达量(P<0.05或P<0.01)。结论依帕司他对血管内膜的增生及再狭窄的形成有抑制作用,伴有AR及NF-кB的表达受抑。更多还原

【Abstract】 Background Accumulating reports showed that aldose reductase(AR)enhances oxidative stress,accelerates cell division and proliferation,activates transcription factors(nuclear factor-κB,NF-кB).The role of AR in vascular vessel restenosis is not certain.Objective This research aims to the explore the inhibition effect of epalrestat(AR inhibitor)on AR expression and intimal hyperplasia in the rat carotid arteries with restenosis.Methods Twenty four healthy male SD rats were grouped randomly into group A(the sham operation group,n=8),group B(the operation group without treatment,n=8),group C(the operation group and treated with epalrestat,n=8).The right carotid arteries were injuried by air-drying operation in group B and group C.The left carotidarteries were served as controls.The rats were sacrified 7 or 14 days after operation and vascular vessels were studied histologically to examine the intimal and the medial hyperplasia.AR and NF-κB expression were examined by FISH in situ hybridization and immunohistochemical methods.Results 1)Seven days after the operation,the intimal hyperplasia was obvious in the injuried sides and aggravated after 14 days.2)Epalrestat obviously inhibited the intimal hyperplasia after the endothelial injuries,decreased intimal thickness and the ratio of the intimal and the medial thickness in relative to the control group B(P<0.05 or P<0.01).3)The expression of AR and NF-κB in the injuried sides was obviously higher than that of the control sides.Epalrestat significantly inhibit the expression of AR and NF-κB(P<0.05 or P<0.01)as well.Conclusion Epalrestat inhibits the vascular vessel neointima proliferation and restenosis associated with attenuation of the expression of AR and NF-κB.更多还原