RAGE调节Wnt/β-catenin信号通路对DM大鼠主动脉保护作用的研究  

Study on the regulatory role of RAGE on Wnt/β-catenin signaling pathway and its protective effect in DM rats aorta

作　　者：陈春莲[1] CHEN Chun-lian(Department of General Practice Affiliated Hospital of Guilin Medical College,Guilin 541001,China)

机构地区：[1]桂林医学院附属医院全科医学,桂林541001

出　　处：《现代免疫学》2020年第5期396-401,共6页Current Immunology

基　　金：四川省教育厅2017年度科研计划项目(17TD0047)。

摘　　要：检测2型糖尿病(type 2 diabetes, D2M)大鼠主动脉组织中Wnt/β-catenin信号通路相关蛋白以及晚期糖基化终末产物受体(receptor for advanced glycation end product, RAGE)表达水平,分析RAGE对Wnt/β-catenin信号通路的调节作用以及对大鼠主动脉病变的影响;检测血脂相关指标水平,分析血脂水平与糖尿病之间的关系。构建D2M大鼠模型,在第2、4、8、12周随机分组大鼠模型并设置空白对照组,检测空腹血糖、血清总胆固醇(serum total cholesterol,TC)、甘油三酯(triglyceride,TG)、高、低密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)(low density lipoprotein-cholesterol,LDL-C)、胰岛素等指标,HE染色观察主动脉组织病理结构;RT-PCR、Western blotting检测主动脉组织Wnt2、β-catenin、T细胞因子4(T cell factor 4,TCF4)、RAGE等相关指标mRNA及蛋白表达情况。结果显示,与空白对照组相比,D2M大鼠TC、TG、LDL-C水平显著升高,HDL-C水平显著下降;D2M大鼠不同时间段与第2周相比,TC、TG、LDL-C水平显著升高,HDL-C水平显著下降(P<0.01,P<0.05)。HE染色显示D2M大鼠主动脉局部内皮细胞发生不同程度的空泡变性或坏死。D2M大鼠在第2周与12 w内主动脉组织Wnt2和β-catenin mRNA及蛋白水平与空白对照组相比差异有统计学意义(P<0.01),8 w后维持在较高水平;TCF4、RAGE水平较空白对照组持续上升(P<0.05);分泌型卷曲相关蛋白2(secreted frizzled-related protein 2,sFRP2)水平较对照组持续下降(P<0.01)。由此,RAGE通过调节Wnt/β-catenin信号通路影响D2M大鼠主动脉相关蛋白表达,可能对相关主动脉病变有保护作用。To detect the expression levels of advanced glycation end product(AGE) and its receptor(RAGE) in aortic tissue of type 2 diabetes(D2 M) rats, and analyze the regulatory effect of RAGE on Wnt/β-catenin signaling pathway and on aortic lesions, we established a D2 M rat model and randomly divided them into model group and blank control group. At weeks 2, 4, 8 and 12, fasting blood glucose(FBG), serum total cholesterol(TC), triglyceride(TG), high and low density lipoprotein-cholesterol(HDL-C, LDL-C), insulin and other indicators in fasting serum were measured, and HE staining was used to observe the pathological structure of aorta;RT-PCR, Western blotting were used to detect the mRNA and protein expressions of aorta Wnt2, β-catenin, T cell factor 4(TCF4), AGE, RAGE and other related indexes. The results showed that compared with the blank control group, the levels of TC, TG, LDL-C in D2 M rats were significantly increased, and the levels of HDL-C were significantly decreased(P<0.01, P<0.05). Compared with the D2 M rats of week 2, TC, TG, LDL-C levels of the D2 M rats at different time stages were significantly increased while HDL-C levels were significantly decreased(P<0.01, P<0.05). HE staining showed that varying degrees of vacuolar degeneration or necrosis occurred in the aorta endothelial cells in the DM group. Compared with the blank control group, the Wnt2, β-catenin mRNA and protein levels in the aortic tissues of the DM rats in the week 2 and within 12 weeks showed statistical significance(P<0.01), and remained at high levels after week 8;The level of TCF4 continued to rise compared with the blank control group(P<0.05);The level of secreted frizzled-related protein 2(sFRP2) continued to decrease compared with the control group(P<0.01). Therefore, by influencing the Wnt/β-catenin signaling pathway, RAGE could regulate the expression of aortic related proteins in DM rats, and may improve related aortic lesions.

关 键 词：Β连环蛋白 糖基化终末产物 2型糖尿病 主动脉损伤 

分 类 号：R587.1[医药卫生—内分泌]