糖尿病载脂蛋白E基因缺陷小鼠动脉粥样硬化斑块炎症反应增强  

Increased Inflammatory Reaction in ApoE Deficient Mice with Diabetes

作　　者：朱旖[1] 徐标[1] 高玲[1] 孟奎[1] 

机构地区：[1]南京大学医学院附属鼓楼医院心脏科,江苏省南京市210008

出　　处：《中国动脉硬化杂志》2008年第5期349-352,共4页Chinese Journal of Arteriosclerosis

基　　金：江苏省自然科学基金(BK2004083)

摘　　要：目的观察伴糖尿病的载脂蛋白E基因缺陷雄性小鼠自发性动脉粥样硬化斑块形态和分子生物学特性的变化。方法链脲霉素60mg/(kg·d)腹腔注射诱导载脂蛋白E基因缺陷雄性小鼠糖尿病组,非糖尿病组给予等量缓冲液注射。饲养14周后处死小鼠,分别于建模前和处死前测定小鼠体重、血清总胆固醇、血糖、血清糖基化终产物水平。应用Westernblot检测主动脉环氧化酶2、前列腺素合成酶微粒体亚单位Ⅰ型、基质金属蛋白酶9、糖基化终产物受体表达水平。应用HE、油红O、天狼星红染色分析斑块面积、脂质、胶原含量。应用免疫组织化学检测斑块内巨噬细胞、T细胞、血管平滑肌细胞α肌动蛋白密度,环氧化酶2、前列腺素合成酶微粒体亚单位Ⅰ型、基质金属蛋白酶9、糖基化终产物受体表达水平。结果与非糖尿病组比较,糖尿病组血清总胆固醇明显增高(P<0.01),血清糖基化终产物增高(P<0.05);糖尿病组斑块面积增大,斑块内巨噬细胞密度、环氧化酶2、前列腺素合成酶微粒体亚单位Ⅰ型表达增多(P<0.05),T细胞密度、脂质含量、糖基化终产物受体、基质金属蛋白酶9表达显著升高(P<0.01),胶原含量、血管平滑肌细胞密度显著降低(P<0.01)。结论载脂蛋白E基因缺陷糖尿病小鼠较非糖尿病小鼠动脉粥样硬化更严重,斑块内炎症反应明显增强,这可能是糖尿病动脉粥样硬化斑块不稳定增加的机制之一。Aim To investigate whether atheroselerofic plaque inflammation is increased and the related mechanisms in atherosclerotic plaques in diabetic apolipoprotein E-deficient mice. Methods Male apolipoproteinE-deficient mice were in-jected with 60 mg/（kg·d）streptozotocin for 5 days to induce diabetes and mice with fasting glucose〉 10 mmol/L were included to diabetic mellitus group （ n = 8）, control mice （n=8） were injected with citrate buffer. The levels of serum total cholesterol, glucose and advanced glycation end-products in apohpoproteinE-deficient mice were dectected in 8 and 22 weeks. The expression of receptor for advanced glycation end-products, cyclooxygenase-2, microsomal prostaglandin E synthase-1 and metalloproteinase-9 were determined by immunohistochemistry and Western blot. Immunohistochemistry was also used to identify CD68 ＋ mac-rophages, CD^3＋ T-lymphocytes, a-smooth muscle actin, CD31^＋ endothclia cells and collagen. Results Compared with control group, diabetic meUitus group had higher serum total cholesterol, glucose （ P 〈 0.01）, and advanced glycafion end-products（P〈0.05） levels. Atheroselerotic plaques in diabetic apolipoprotein E-deficient had larger area and more macrophages, cy-clooxygenase-2, mierosomal prostaglandin E synthase-1（P〈0.05）, Lipid, T-lymphoeytes, receptor for advanced glyeation end-products, and metalloproteinase-9 （P〈0.01）, reduced or-smooth muscle aetin and collagen content （p〈0.01）. Conclusions These data suggest that diabetes meUitus is associated with enhanced inflammatory reaction, and these changes may cont- ribute to increased instabability in diabetic plaques.

关 键 词：病理学与病理生理学 糖尿病 不稳定斑块 炎症 动脉粥样硬化 载脂蛋白E基因缺陷小鼠 糖基化终产物 

分 类 号：R363[医药卫生—病理学]