糖尿病性下肢动脉硬化斑块不稳定因素的初步研究

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1、中图分类号：R658.3；R654.4硕士学位论文糖尿病性下肢动脉硬化斑块不稳定因素的初步研究院（系）、所临床医学院研究生姓名龙万平学科、专业外科学导师姓名何延政教授二Ο一二年四月目录1糖尿病性下肢动脉硬化斑块不稳定因素的初步研究„„„„„„„„„„„„„„„„„„„„„„„„11.1中文摘要„„„„„„„„„„„„„„„„„„„„„11.2英文摘要„„„„„„„„„„„„„„„„„„„„„31.3前言„„„„„„„„„„„„„„„„„„„„„„„51.4材料与方法„„„„„„„„„„„„„„„„„„„„81.5结果„„„„„„„„„„„„„„„„„„„„„„„181.6讨论„„„„„„„„„

2、„„„„„„„„„„„„„„311.7结论„„„„„„„„„„„„„„„„„„„„„„„391.8参考文献„„„„„„„„„„„„„„„„„„„„„401.9英汉缩略词对照表„„„„„„„„„„„„„„„„„452致谢„„„„„„„„„„„„„„„„„„„„„„„463miRNA在动脉粥样硬化病变中作用研究进展（综述）„„„„„„„„„„„„„„„„„„„„„„„47糖尿病性动脉硬化粥样斑块不稳定因素的初步研究摘要目的：终末糖基化产物（advancedglycationendproducts,AGE）在糖尿病性血管并发症中起着重要作用，而基质金属蛋白酶（matrixmetalloprotein

3、ases,MMPs）与斑块的不稳定密切相关。本研究通过比较2型糖尿病患者与非糖尿病患者下肢离体动脉粥样硬化标本中斑块内AGE及其受体（receptorforAGE，RAGE）、MMP-2（matrixmetalloproteinase-2）的表达情况的差异，探讨其关联。通过检测斑+块内CD68巨噬细胞的表达、细胞外基质(extracellularmatrix，ECM)厚度、平滑肌细胞凋亡表达与RAGE表达的关联，探讨其相关性斑块不稳定的机制。方法：本实验对纳入研究的2型糖尿病和非糖尿病患者离体下肢动脉粥样硬化斑块标本各8例应用HE染色进行斑块形态学检测+并初步病理分析。免疫组化SABC法检测A

4、GE、RAGE、MMP-2、CD68巨噬细胞在斑块内的表达情况。Masson染色法检测斑块处ECM的表达情况。TUNEL染色法检测斑块内细胞凋亡情况。结果：在糖尿病性斑块内AGE蓄积的面积，RAGE、MMP-2阳性表达区域的范围均较非糖尿病性斑块显著增大，两者间差异均有统计学意义(P＜0.05)。RAGE、MMP-2的表达与AGE的蓄积之间呈直线正相关关系，与ECM的表达呈直线负相关关系。血浆HbA1c水平也与AGE蓄积、MMP-2的表达，RAGE的表达，细胞凋亡正相关。RAGE高表达区域较相对低表达区域比较具有更多斑块不稳定特+征：斑块面积更大，脂质核心占斑块面积更大；CD68巨噬细胞阳性表

5、达1更多；平滑肌凋亡（阳性）细胞更多。结论：目前的研究表明AGE通过RAGE途径参与了动脉硬化斑块内MMP-2表达、炎症的放大及细胞凋亡的发生，并导致了斑块的不稳定性，与糖尿病性急性血管并发症相关。关键词：外周动脉疾病，AGE，RAGE，MMP-2，临床病理特征，易损性斑块2Prelininarystudyoftheunstabilityfactorsofatherosclerosisplaquesinhumanatherosclemticwithtype2diabetesAbstract：Objective：AGE（advancedglycationendproducts，AGE）playa

6、keyroleindiabeticvascularcomplications,whereasMMPs（matrixmetalloproteinases）contributetoplaqueinstability.ThisstudywasconductedtoinvestigatethedifferencesexpressionofAGE，RAGE，ECMandMMP-2intheextentofatheroscleroticplaquespecimensoflowerextremityarteriesofpatientswithorwithouttype2diabeties,exploreit

7、saffiliates.Through+detectiontheproportionsofMMP-2expression，CD68macrophagesexpressionandapoptosisinintimalareasassociationwithRAGEexpression，Toinvestigatethemechanismsunderlyingatheroscleroticplaques