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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。
AIM To investigate the effect of rosiglitazone on the expression of LRP-1 in brain micro / small vessels of diabetic rats with different course of diabetes and the effect of rosiglitazone on the expression of beta-amyloid (Aβ1-40) mechanism. Methods Spontaneous type 2 diabetic rats (GK rats) were used as animal models, which were divided into 2 groups of 6 months and 3 months according to their duration of disease. The 6-month-old rats were randomly divided into two groups: DM6RSG group), non-intervention group (DM6 group), and 3-month-old GK rats (DM3 group) as the course of disease course. Immunohistochemical localization of Aβ1-40 and LRP-1 The expression of Aβ1-40 and LRP-1 protein in each group were detected by enzyme-linked immunosorbent assay (ELISA). The expression of LRP-1 mRNA in brain tissue was detected by RT-PCR. Results Compared with DM3 group, the expression of Aβ1-40 in DM6 group was significantly increased (P <0.01). Compared with DM6 group, the expression of Aβ1-40 in DM6RSG group was significantly decreased (P <0.01), LRP-1 and LRP-1 mRNA (P <0.05). Conclusions With the development of diabetes mellitus, the deposition of Aβ1-40 in brain micro / small vessels increased significantly. Rosiglitazone up-regulated the expression of LRP-1 and LRP-1 mRNA and decreased the expression of Aβ1-40 in micro / small vessels of diabetic brain Deposition.