晚期糖基化终产物受体在糖尿病大鼠自体移植静脉中的表达及氨基胍的干预作用  

Expression of Receptor of Advanced Glycation End Products and Effect of Aminoguanidine on Intimal Hyperplasia in Autogenous Vein Graft of Rats with Streptozotocin Induced Diabetes

作　　者：王欣[1] 张强[1] 张宏伟[1] 霍鑫[1] 杜惠莲[2] 

机构地区：[1]中国医科大学附属第一医院干诊科,沈阳110001 [2]沈阳医学院附属卫校,沈阳110043

出　　处：《中国普外基础与临床杂志》2008年第6期390-395,共6页Chinese Journal of Bases and Clinics In General Surgery

摘　　要：目的探讨晚期糖基化终产物受体(RAGE)在糖尿病大鼠自体移植静脉中的表达及氨基胍对其内膜增生的干预作用。方法雄性SD大鼠60只,随机均分为氨基胍组、蒸馏水组及对照组,前2组行链脲佐菌素腹腔注射建立糖尿病模型,并分别用氨基胍或蒸馏水灌胃,对照组为未作处理的正常大鼠。3组均建立自体静脉移植模型后,于术后第7d及14d测定血清晚期糖基化终产物(AGE)含量,同时取自体静脉移植标本进行组织形态学观察,Westernblot和免疫组织化学染色方法检测RAGE及NF-κBp65的蛋白表达,半定量RT-PCR检测RAGE及NF-κBp65mRNA的表达。结果术后第7d及14d,相对于对照组大鼠,蒸馏水组糖尿病大鼠自体移植静脉内膜增生加重,血清AGE含量增加,RAGE和NF-κBp65mRNA和蛋白表达增强,差异均有统计学意义(P<0.05);氨基胍组血清AGE含量、NF-κBp65蛋白和mRNA表达及内膜增生均较蒸馏水组减少或减轻(P<0.05),与对照组相比差异无统计学意义(P<0.05)。结论糖尿病大鼠自体移植静脉RAGE表达增强,激活NF-κB,与移植静脉内膜增生关系密切;氨基胍抑制AGE的产生,可阻断AGE-RAGE结合,减轻内膜增生。Objective To study the expression of receptor of advanced glycation end products （RAGE） in autogenous vein graft of streptozotocin induced diabetic rats and the inhibitory effects of aminoguanidine on intimal hyperplasia. Methods Sixty male Sprague-Dawley rats were randomly divided into three groups： aminoguanidine group, distilled water group and control group. Autogenous vein graft models were established in all groups. Streptozotocin was injected into abdominal cavity to induce diabetes in both aminoguanidine group and distilled water group, and they were intragastric administrated with aminoguanidine or distilled water, respectively before and after transplantation. Specimens were collected from autogenous vein graft 7 days and 14 days after surgery to undergo histological examination. At the same time, the level of serum advanced glycation end products （AGE） was tested. Western blotting and immunohistochemistry were used to detect the protein expression of RAGE and NF-kB p65. RAGE and NF-kB p65 mRNA were measured by reverse transcription-PCR. Results The mRNA and protein expressions of RAGE, NF-kB p65, the level of serum AGE and the intimal thickness of vein graft in distilled water group increased in comparison with those in control group 7 days and 14 days after surgery （P〈0.05）. The level of serum AGE, mRNA and protein expressions of NF-kB p65 and the intimal thickness of vein graft in aminoguanidine group were lower than those in distilled water group （P〈0.05）, and showed no significant difference compared with control group （P〉0.05）. Conclusion The over-expression of RAGE in vein graft activats NF-kB in streptozotocininduced diabetic rat, which has a close relation with intimal hyperplasia. Aminoguanidine can block the binding of AGE and RAGE by inhibiting the production of AGE, which will prevent intimal hyperplasia of vein graft.

关 键 词：晚期糖基化终产物 受体 增生 氨基胍 静脉移植物 

分 类 号：R587.1[医药卫生—内分泌] R654.3[医药卫生—内科学]