Catalpol Prevents Glomerular Angiogenesis Induced by Advanced Glycation End Products via Inhibiting Galectin-3  

作　　者：Wei-xiang SUN Yu-yan GAO Ying CAO Jin-fu LU Gao-hong LV Hui-qin XU 

机构地区：[1]Jiangsu Key Laboratory for High-Tech Research and Development of Veterinary Biopharmaceuticals,Jiangsu Agri-animal Husbandry Vocational College,Taizhou 225300,China [2]Department of Chinese Pharmaceutical Technology,School of Animal Pharmacy,Jiangsu Agri-animal Husbandry Vocational College,Taizhou 225300,China [3]Department of Pharmacology,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China [4]Jiangsu Key laboratory of Pharmacology and Safety Evaluation for Chinese Material Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China [5]Department of Pharmacology,School of Pharmacy,Nanjing University of Chinese Medicine Hanlin College,Taizhou 225300,China

出　　处：《Current Medical Science》2023年第4期668-678,共11页当代医学科学（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(No.81374029,No.81073111,No.81874359);Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.18KJD360002);a Project Funded by Jiangsu Agri-animal Husbandry Vocational College(No.NSF2021CB04);a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(No.JKLPSE201604).

摘　　要：Objective:The main characteristics of diabetic nephropathy(DN)at the early stage are abnormal angiogenesis of glomerular endothelial cells(GECs)and macrophage infiltration.Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand,advanced glycation end products(AGEs).Catalpol,an iridoid glucoside extracted from Rehmannia glutinosa,has been found to ameliorate vascular inflammation,reduce endothelial permeability,and protect against endothelial damage in diabetic milieu.However,little is known about whether catalpol could exert an anti-angiogenesis and anti-inflammation effect induced by AGEs.Methods:Mouse GECs(mGECs)and RAW 264.7 macrophages were treated with different concentrations of AGEs(0,50,100,200 and 400μg/mL)for different time(0,6,12,24 and 48 h)to determine the optimal concentration of AGEs and treatment time.Cells were treated with catalpol(10μmol/L),GB1107(1μmol/L,galectin-3 inhibitor),PX-478(50μmol/L,HIF-1αinhibitor),adenovirus-green fluorescent protein(Ad-GFP)[3×10^(7)plaque-forming unit(PFU)/mL]or Ad-galectin-3-GFP(2×10^(8)PFU/mL),which was followed by incubation with 50μg/mL AGEs.The levels of galectin-3,vascular endothelial growth factor A(VEGFA)and pro-angiogenic factors angiopoietin-1(Ang-1),angiopoietin-2(Ang-2),tunica interna endothelial cell kinase-2(Tie-2)were detected by enzyme-linked immunosorbent assay(ELISA).Cell counting kit-8(CCK-8)assay was used to evaluate the proliferation of these cells.The expression levels of galectin-3,vascular endothelial growth factor receptor 1(VEGFR1),VEGFR2,and hypoxia-inducible factor-1α(HIF-1α)in mGECs and those of galectin-3 and HIF-1αin RAW 264.7 macrophages were detected by Western blotting and immunofluorescence(IF)staining.The rat DN model was established.Catalpol(100 mg/kg)or GB1107(10 mg/kg)was administered intragastrically once a day for 12 weeks.Ad-galectin-3-GFP(6×10^(7)PFU/mL,0.5 mL)or Ad-GFP(6×10^(6)PFU/mL,0.5 mL)was injected into the tail vein of rats 48 h before the sacrifice of the animals.The expre

关 键 词：CATALPOL glomerular angiogenesis advanced glycation end products GALECTIN-3 

分 类 号：R587.1[医药卫生—内分泌]