摘要
目的 研究核转录因子 κB(NF κB)抑制剂吡咯烷二硫代氨基甲酸酯 (PDTC)对移植静脉内膜增生的影响。方法 Wistar大鼠 64只 ,建立自体静脉移植模型 ,随机分为 4组 :对照组、阴性对照组、PDTC 5 0mg/kg组、PDTC 2 0 0mg/kg组。实验组腹腔注射不同剂量的PDTC连续 3d ,对照组给以生理盐水或不予处理 ;分别在术后 1、2周取材 ,比较内膜增生程度 ;逆转录 多聚酶链反应 (RT PCR)检测NF κBp65mRNA及细胞间粘附分子 (ICAM) 1mRNA的表达 ,原位杂交定位ICAM 1的mRNA表达 ,Westernblot和免疫组织化学方法检测 p65、ICAM 1蛋白产物表达。结果PDTC明显抑制内膜增生 (P <0 .0 5 ) ,2 0 0mg/kg组受抑制程度明显 ,与 5 0mg/kg组比较差异有显著性 (P <0 .0 5 ) ,抑制率 3 1%～ 5 4%。PDTC能够抑制 p65及ICAM 1的mRNA表达 (P <0 .0 1) ,p65和ICAM 1蛋白表达也显著低于各对照组 (P <0 .0 1) ,抑制率 44 %～ 68%。 结论 PDTC可显著抑制移植静脉内膜增生 ,其作用机制可能是通过抑制核转录因子 κB激活、减少黏附分子基因及蛋白产物表达而实现的。
Objective To investigate the effect of nuclear transcription factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) on the intimal hyperplasia (IH) after vein graft in rats.Methods Autogenous vein graft model was established in 64 Wistar rats,transplanting the interior jugular vein to common jugular artery by microsurgical technique.The rats were divided into 4 groups according to the different processing methods,including PDTC 50 mg/kg and 100 mg/kg group,control group and saline group.Samples of vein graft were harvested on the first week and second week after surgery.NF-κBp65 mRNA and intercellular adhesive molecular (ICAM)-1 mRNA were measured by RT-PCR.The position of ICAM-1 mRNA expression was detected by in situ hybridization.Western blotting and immunohistochemistry also were used to detect the expression of p65 and ICAM-1.The IH was compared at the same time.Results The expression of NF-κBp65 mRNA and ICAM-1 mRNA was inhibited significantly by PDTC (P<0.01).Expression of ICAM-1 and p65 was decreased significantly (44% to 68%,P<0.01).The IH was inhibited significantly (31%～54%,P<0.05) in a dose-dependant manner.Conclusion As the inhibitor of NF-κB,PDTC can inhibit IH after vein grafts,which might be accomplished by inhibition of ICAM-1 expression through inhibiting the activation of NF-κB.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2003年第7期602-604,T001,共4页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金资助项目 ( 30 0 0 0 16 3)
