晚期糖基化终产物增加动脉粥样硬化病变部位的炎症反应  

Advanced glycosylation end products increase cellular inflammation in atherosclerotic plaques

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

机构地区：[1]南方医科大学(原第一军医大学)南方医院肾内科,广州510515

出　　处：《中华肾脏病杂志》2005年第6期360-363,共4页Chinese Journal of Nephrology

基　　金：国家自然科学基金重点项目(30330300)国家自然科学基金(30470806)

摘　　要：目的通过整体模型探讨晚期糖基化终产物(AGEs)负荷对动脉粥样硬化斑块炎症反应程度的影响。方法50只新西兰白兔随机分为5组。A组:喂饲高胆固醇饲料,同时注射AGEs修饰的兔血清白蛋白(AGEs—RSA);B组:喂饲高胆固醇饲料,同时注射未加修饰的兔血清白蛋白(RSA);C组:单纯喂饲高胆固醇饲料;D组:喂饲普通饲料;E组:喂饲普通饲料,同时注射AGEs—RSA。10周后分离主动脉全段,油红O染色测定主动脉粥样斑块内脂质含量;免疫组化法计数斑块内浸润的巨噬细胞、T淋巴细胞以及平滑肌细胞的迁移增生。结果喂饲高胆固醇饲料各组动物主动脉均可见粥样硬化斑块形成,斑块病变部位可见不同程度的脂质沉积、巨噬细胞、T淋巴细胞浸润及平滑肌细胞迁移增生。A组粥样斑块中脂质含量[(71.86±8.30)%]显著多于B组[(53.76±3.72)%]和C组[(56.67±9.20)%](P<0.05);粥样硬化斑块病变部位浸润的巨噬细胞[(23.1±8.5)个/0.01 mm2]、T淋巴细胞[(15.1±3.8)个/0.01 mm2]和平滑肌细胞[(19.2±5.7)个/0.01.mm2]较B组[巨噬细胞(14.4±5.9)个/0.01 mm2、T淋巴细胞(9.1±2.6)个/0.01 mm2、平滑肌细胞(12.9±3.8)个/0.01mm2]和C组[巨噬细胞(15.4±4.4)个/0.01mm2、T淋巴细胞(10.5±2.2) 个/0.01 mm2、平滑肌细胞(13.8±3.9)个/0.01Objective To test the hypothesis that advanced glycosylation end products(AGEs) increase cellular inflammation in atherosclerotic plaques. Methods Fifty rabbits were randomly divided into five groups. Hypercholesterolemic (0.5% cholesterol in diet) rabbits received repeated intravenous injection of either AGEs modified rabbit serum albumin (AGEs-RSA ) (group A) or unmodified RSA (group B) for 10 weeks. Rabbits treated with either hypercholesterolemic diet (group C)or with a normal diet(group D) or with a normal diet, and intravenous injection of AGEs-RSA (group E) were served as controls. Aortas were harvested at the 10th week, and lipid deposition was quantitated by oil red 0 staining. Macrophage (RAM-11 positive cells) and T lymphocyte (CD43 positive cells) infiltration, smooth muscle cell(α-actin positive cells) migration and proliferation were determined by using immunohistochemical staining and image-analysis techniques. Results Atherosclerotic plaques could be found in animals fed with hypercholesterolemic diet.Lipid deposition in plaque was significantly higher in group A (71.86%±8.3%) than those in group B (53.76%±3.72%)and group C (56.67%±9.2%). Infiltrations of macrophage[ (23.1±8.5)/0.01 mm2]and T lymphocyte[ (15.1 ± 3.8)/0.01 mm2]as well as migration and proliferation of smooth muscle cell [ (19.2±5.7)/0,01 mm2] in atherosclerotic lesions were significantly increased in animals treated with hypercholesterolemic diet and received injection of AGEs-RSA (group A) when compared with group B [macrophage (14.4± 5.9)70.01 mm2; T lymphocyte (9.1±2.6)/0.01 mm2; smooth muscle cell (12.9±3.8)/0.01 mm2]and group C[macrophage (15.4±4.4)/0.01 mm2; T lymphocyte (10.5±2.2)/0.01 mm2, smooth muscle cell (13.8±3.9)/0.01 mm2]. Neither plaque nor a cellular inflammation was found in animals fed with normal diet (group D)and in those received repeated injections of AGEs-RSA (group E). Conclusion AGEs increase cellular inflammation in atherosclerotic plaques and may accelerate formation of atherosclerosis in AG

关 键 词：炎症反应 病变部位 晚期糖基化终产物(AGEs) 动脉粥样硬化斑块 高胆固醇饲料 平滑肌细胞 T淋巴细胞 动脉粥样硬化病变 淋巴细胞浸润 主动脉粥样斑块 巨噬细胞 血清白蛋白 脂质含量 斑块形成 脂质沉积 新西兰白兔 免疫组化法 

分 类 号：R587.2[医药卫生—内分泌] R543.5[医药卫生—内科学]