糖化和氧化产物修饰的蛋白质促进兔主动脉粥样斑块形成  

Proteins modified with glycation or oxidation products accelerate atherosclerosis in experimental hypercholesterolemic rabbits

作　　者：郭志坚[1] 侯凡凡[1] 刘尚喜[1] 张卫茹[1] 周展眉[1] 刘志强[1] 

机构地区：[1]第一军医大学南方医院肾内科,广州510515

出　　处：《北京大学学报（医学版）》2004年第2期127-130,共4页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金重点项目 ( 3 0 3 3 0 3 0 0 ) ;国家自然科学基金 ( 3 0 2 70 62 2 ) ;广东省团队项目 ( 10 717) ;广东省自然科学基金重点项目 ( 0 13 0 76)~~

摘　　要：目的 :探讨晚期糖基化终产物 (AGE)和晚期蛋白质氧化产物 (AOPP)对动脉粥样硬化斑块形成的影响。方法 :5 0只 1 2周龄新西兰白兔被随机分为 5组 (每组 1 0只 ) ,除对照组外均以高胆固醇饲料喂养并分别注射或不注射兔血清白蛋白及AGE或AOPP修饰的兔血清白蛋白。 1 0周后处死动物 ,取血清测血脂、AGE和AOPP水平 ;取主动脉全段 ,以苏丹IV染色 ,PHOTOSHOP○R软件分析粥样斑块占主动脉壁的相对面积 ;显微镜下测量粥样斑块的平均厚度。结果 :(1 )AGE和AOPP组主动脉全段的动脉粥样斑块相对面积 (5 0 .1 %± 7.4 %和 6 2 .4 %±8.8% )均明显大于单纯胆固醇喂饲组 (2 9.8%± 6 .3% )和白蛋白组 (2 0 .9%± 6 .4 % ) (P均 <0 .0 5 )。 (2 )AGE和AOPP组胸主动脉段粥样斑块的平均厚度 [(1 4 7.7± 1 3.1 ) μm和 (1 38.1± 1 3.0 ) μm]均明显大于单纯胆固醇喂饲组 [(85 .7± 1 5 .0 ) μm和白蛋白组 [(95 .5± 1 5 .7) μm](P均 <0 .0 5 ) ;(3) 4个喂饲高胆固醇饲料组的血脂水平无明显差异 ,注射AGE或AOPP的动物血清中AGE或AOPP水平明显增高 ,且与斑块相对面积呈正相关 (AGE与斑块相对面积 :r=0 .4 0 8,P =0 .0 0 5 ;AOPP与斑块相对面积 :r =0 .5 95 ,P =0 .0 0 0 )。结论 :AGE和AOPP促进高胆固醇动物动脉粥样斑块?Objective:To investigate whether advanced glycation end products (AGE) or advanced oxidative protein products (AOPP) contributes to atherogenesis in experimental hypercholesterolemic rabbits. Methods: Hypercholesterolemic (0.5% wt/wt diet) rabbits received repeated intravenous injections of either AGE modified rabbit serum albumin (AGE RSA) or AOPP modified RSA (AOPP RSA) for 10 weeks. Three control groups were set as follows: a group fed with high cholesterol diet alone, a group fed with high cholesterol diet and injected with normal RSA, and a group fed with normal diet. The animals were sacrificed and aortas were dissected and stained with Sudan red IV. Atheromatous plaques in the aortas en face were evaluated by computer assisted morphometry and by histologic examination. Hematological parameters (triglyceride, cholesterol, AGE and AOPP) were also tested. Results:(1) The relative plaque area in rabbits receiving repeated injections of AGE or AOPP was 50.1%±7.4% and 62.4%±8.8% respectively, both were significantly larger than either that of hypercholesterolemic rabbits (29.8%±6.3%, P <0.05) or that of hypercholesterolemic rabbits injected with unmodified RSA (20.9%±6.4%, P <0.05). In aortic arch, thoracic aorta and abdominal aorta, atherosclerotic lesions in AGE group and AOPP group were more severe than in any of the control groups. (2)The average thickness of the plaques on thoracic aortas in AGE group [(138.1 ±13.0 )μm] and in AOPP group [(147.7± 13.1) μm ]were significantly thicker than either of that in the group treated with hypercholesterolemic diet alone [(85.7±15.0) μm ]or that in the group treated with non modified RSA [(95.5±15.7) μm]. (3) Glycereide and cholesterol levels in all animals on hypercholesterolemic diet were similar. AGE and AOPP serum levels in groups injected with AGE or AOPP were significantly higher thanthat in any of the control groups. AGE serum concentrations were positively correlated with the atheromatous plaque area( r =0.408, P =0.005)

关 键 词：糖基化终产物 蛋白质氧化产物 动脉粥样硬化 血清白蛋白 动物模型 慢性肾功能衰竭 

分 类 号：R543.5[医药卫生—心血管疾病]