罗格列酮经LRP-1途径降低糖尿病大鼠脑微／小血管中β-淀粉样蛋白含量的研究  

Effects of rosiglitazone on amyloid-beta peptide clearance from brain micro/small vessels by regulation of LRP-1 in diabetic rats

作　　者：胥文娟[1] 朱梅佳[2] 赵张宁[2] 孙忠文[1] 鲍梦馨[1] 

机构地区：[1]山东大学,医学院,济南250012 [2]山东大学,附属千佛山医院神经内科,济南250014

出　　处：《山东大学学报（医学版）》2012年第6期5-9,13,共6页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金资助项目(ZR2010HM101);山东省科技攻关基金资助项目(2007GGWZ02056)

摘　　要：目的研究罗格列酮对不同病程糖尿病大鼠脑微/小血管中低密度脂蛋白受体相关蛋白-1(LRP-1)表达的影响及其清除β-淀粉样蛋白(Aβ1-40)的机制。方法采用自发性2型糖尿病大鼠(GK大鼠)作为动物模型,将其按病程分为6月龄及3月龄2组,其中6月龄组再随机分为罗格列酮干预组(DM6RSG组)和非干预组(DM6组),3月龄GK大鼠(DM3组)作为病程对照组;采用免疫组织化学法定位检测各组脑微/小血管上Aβ1-40及LRP-1的表达,酶联免疫吸附法(ELISA)检测各组脑组织中Aβ1-40及LRP-1蛋白的表达量,RT-PCR定量检测脑组织中LRP-1mRNA的表达。结果与DM3组相比,DM6组Aβ1-40的表达明显增加(P<0.01);与DM6组相比,DM6RSG组Aβ1-40的表达明显减少(P<0.01),LRP-1和LRP-1mRNA的表达均明显增加(P均<0.05)。结论随糖尿病病程增长,Aβ1-40在脑微/小血管中沉积明显增多,罗格列酮可上调LRP-1和LRP-1mRNA的表达并明显减少Aβ1-40在糖尿病脑组织微/小血管中的沉积。Abstract： Objective To investigate the effects of rosiglitazone on expression of low-density lipoprotein receptor-related protein 1 （LRP-1） and the clearance mechanism of 40-amino-acid form of amyloid beta （Aβ1-40） in brain micro/ small vessels in different courses of diabetic rats. Methods Goto-Kakizaki （GK） rats were used as type 2 diabetic models. The GK rats were randomly divided into three groups： the 3-month-old GK rats group （DM3 group）, the 6- month-old GK rats group （DM6 group） and the DM6 treated with rosiglitazone group （DM6RSG group）. The DM3 group also acted as the control group. Expressions of Aβ1-40and LRP-1 were detected by immunohistochemistry and enzyme-linked immunosorbent assays （ELISA）. Expressions of LRP-lmRNA were detected by RT-PCR. Results Compared to that of the DM3 group, expression of Aβ1-40 in the brain tissue was higher in the DM6 group （ P 〈 0.01 ）. Compared to those of the DM6 group, expressions of LRP-I and LRP-lmRNA in the brain tissue were higher in the DM6RSG group （P 〈 0.05 ）, however, expression of Aβ1-40 in the brain tissue was lower in the DM6RSG group than that of the DM6 group （ P 〈 0.01 ）. Conclusion With diabetes mellitus progression, the deposition of Aβ1-40 in brain micro/small vessels significantly increases. Rosiglitazone can up-regulate expressions of LRP-1 and LRP-lmRNA and then decrease the deposition of Aβ1-40 in diabetic brain tissue micro/small vessels.

关 键 词：糖尿病 大鼠 淀粉样Β蛋白 LDL受体相关蛋白质1 过氧化物酶增殖体激活受体Γ 

分 类 号：R743.3[医药卫生—神经病学与精神病学]