ABSTRACT
Objective To observe the effect of liraglutide on arteriosclerotic lesions in diabetic ApoE- / - mice via regulating receptor for advanced glycation end-products ( RAGE) expression of aorta. Methods Thirty male ApoE- / - mice (10 weeks) were randomly divided into 3 groups: control group, diabetes group, and diabetes +liraglutide group. All the mice were fed a high-fat diet. Diabetes was induced by 2 intraperitoneal injection of streptozotocin (STZ, 55 mg·kg-1 ·d-1 ). Mice were treated with subcutaneous injection of liraglutide (0. 4 mg· kg-1 ·d-1 ) in diabetes+liraglutide group. After 9 weeks, blood was drawn and the aorta were rapidly procured. The serum levels of advanced glycation end-products ( AGEs), soluble receptor for advanced glycation end-products (sRAGE ), stromal cell-derived factor-1α ( SDF-1α ), as well as total cholesterol and triacylglycerol were measured. Atherosclerotic plaque area was determined by Sudan Ⅳ staining. The expression of RAGE was determined using RT-PCR and western blot, respectively. Results Compared with control group, the serum AGEs, the RAGE protein and mRNA expression, the atherosclerotic lesions were significantly increased in the mice of diabetes group. Compared with diabetes group, the serum AGEs, the RAGE protein and mRNA expression, the atherosclerotic lesions were significantly decreased in the mice of diabetes+liraglutide group. Conclusion Liraglutide is confirmed as to have an anti-atherosclerotic effects and inhibits RAGE expression in diabetic ApoE- / - mice.
ABSTRACT
Objective To investigate the role of high mobility group box 1 protein(HMGB1) and the receptor for advanced glycation end products (RAGE) in the pathogenesis of primary gouty arthritis (GA).Methods Enzyme-linked immunosorbent assay(ELISA) was used to determine the level of plasma HMGB1 in 68 acute gout (AG),48 quiescent gout (QG) and 45 healthy control(HC).Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure the expression of HMGB1 and RAGE mRNA in the peripheral blood mononuclear cells (PBMCs) in 68 AG,48 QG and 94 HC.One way ANOVA or Wilcoxon test and Spearman's correlations were used for statistical analysis.Results The level of plasma HMGB1,PBMCs HMGB1 and RAGE mRNA were significantly higher in GA than that in HC [(24±34) ng/ml,0.019±0.029,0.000 5±0.000 3] (P＜0.05),while the level of plasma HMGB1 and PBMCs HMGB1 mRNA were significantly higher in AG [(222±178) ng/ml,0.235±0.954,0.001 5±0.003 5] than that in QG [(107±176) ng/ml,0.044±0.117,0.001 3±0.000 9] (P＜0.05),and the level of PBMCs RAGE mRNA was higher in AG than that in QG (P＞0.05).In the GA patients,the level of plasma HMGB1 was positively correlated with white blood cell count,neutrophile granulocytes count,mononuclear cells and erythrocyte sedimentation rate (r=0.34,0.44,0.39,0.33; P＜0.05),while negatively correlated with apolipoprotein A1 (r=-0.28,P＜0.05); the level of PBMCs HMGB1 mRNA was positively correlated with RAGE mRNA,white blood cell counts,neutrophil counts,lymphocyte counts,serum total cholesterol level,low density lipoprotein level and apolipoprotein B100 level (r=0.29,0.36,0.26,0.28,0.29; P＜0.05),while negatively correlated with high density lipoprotein (r=-0.30,P＜0.01); the level of PBMCs RAGE mRNA was positively correlated with lymphocyte counts,total cholesterol and apolipoprotein B100 (r=0.35,0.35,0.44; P＜0.05).Conclusion HMGB1 and its signaling pathway may play important role in the pathogenesis of gouty arthritis,which may also be involved in the regulation of the lipid metabolism of gout.
ABSTRACT
Receptor for advanced glycosylation end products (RAGE) has long been a focus in studies of diabetic vascular diseases. Recently, clinical evidence has shown that the expression level of RAGE is high in liver, stomach, pancreas and prostate cancer tissues whereas the expression level of RAGE is lower in chondrosarcoma and lung cancer tissues. The abnormal expression of RAGE is closely associated with tumorgenesis, angiogenesis, tumor invasion and metastasis. This review summarizes the abnormal expression of RAGE in different tumors and its role in carcinogenesis and development of tumor. Copyright© 2011 by TUMOR.