糖尿病对大鼠自体移植静脉内膜增生的影响

The effect of diabetes mellitus on intimal hyperplasia in autogenous vein graft of rats

目的探讨AGE-RAGE系统对糖尿病大鼠自体移植静脉内膜增生的作用。方法雄性SD大鼠40只,随机分为糖尿病组及正常对照组。两组均建立自体静脉移植模型,制模后的7d和14d测定血清AGE含量,取自体静脉移植标本行组织形态学观察,半定量RT-PCR检测RAGE,NF-κBp65及VCAM-1mRNA的表达,Western蛋白印迹和免疫组化方法检测RAGE,NF-κBp65及VCAM-1蛋白表达,并用免疫组化方法检测PCNA的表达。结果术后7d及14d,与对照组比较,糖尿病组自体移植静脉内膜增生明显为重,PCNA,RAGE,NF-κBp65及VCAM-1mRNA和蛋白表达均增强,血清AGE含量增加,差异均有统计学意义(均P<0.05)。结论AGE-RAGE系统激活NF-κB,增强黏附分子的表达,可能是糖尿病大鼠自体移植静脉内膜增生加重的原因。

Objective To investigate the role of AGE-RAGE system on intimal hyperplasia in autogenous vein graft of diabetic rats. Methods The experiments were performed on 40 male Sprague-Dawley rats which divided into two groups： diabetes group and control group. Autogenous vein graft model was established in all rats. Specimens were harvested 7 days and 14 days after surgery for histological examination, and RAGE, NF-κB p65 and VCAM-1 mRNA were measured by semi-quantitative reverse transcription-PCR. Western Blotting and immunohistochemistry were used to detect the protein expression of RAGE, NF-κB p65 and VCAM-1. At the same time, the levels of serum AGE were tested. Results Compared with non-diabetic rats of control group, the intimal hyperplasia of vein graft in diabetic rats obviously increased （ P 〈 0.05 ）. At the same time, the mRNA and protein expression of RAGE, NF-κB p65 and VCAM-1 obviously increased （ P 〈 0.05 ） , and the level of the serum AGE obviously increased （ P 〈 0.05 ）. Conclusions AGE-RAGE system activated NF-κB and enhanced the expression of VCAM-1 , which might be the cause of increased intimal hyperplasia in autogenous vein graft of diabetic rats.