Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway  

作　　者：LV Xing LV Gao-Hong DAI Guo-Ying SUN Hong-Mei XU Hui-Qin 

机构地区：[1]Department of Pharmacology,College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China [2]Jiang Su key Laboratory for Efficacy and Safety Evaluation of Chinese Medicine,Nanjing 210023,China [3]Department of Chinese Medicine Resources,College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China

出　　处：《Chinese Journal of Natural Medicines》2016年第11期844-855,共12页中国天然药物（英文版）

基　　金：supported by National Nature Science Foundation of China(No.81073111);the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.nzyzyxjp1006);Jiangsu Province graduate student scientific research innovation plan project(No.CXZZ13_0622)

摘　　要：The aim of this study was to investigate the effects of high-advanced glycation end products （AGEs） diet on diabetic vascular complications. The Streptozocin （STZ）-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators 3f renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic sharacteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein （CRP）, low density lipoprotein （LDL）, tumor necrosis factor-a （TNF-a）, and interleukin-6 （IL-6） in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial ceils, mesangial cells and podocytes in renal ：ortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species ＇,ROS） and low-levels of superoxide dismutase （SOD） in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.The aim of this study was to investigate the effects of high-advanced glycation end products(AGEs) diet on diabetic vascular complications. The Streptozocin(STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia,polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein(CRP), low density lipoprotein(LDL), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species(ROS) and low-levels of superoxide dismutase(SOD) in serum, heart, and kidneys. It also upregulated RAGE mR NA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

关 键 词：Advanced glycation end products Diabetic vascular complications AGEs/RAGE/ROS pathway c-Reactive protein leactive oxygen species 

分 类 号：R965[医药卫生—药理学]