title: Astragaloside IV ameliorates diabetic nephropathy involving protection of podocytes in streptozotocin induced diabetic rats.
abstract: Podocyte loss and dysfunction play key role during the development of diabetic nephropathy (DN). The aim of this study was to observe the protective effects of astragaloside IV on podocyte in diabetic rats and explore its mechanisms preliminary. Healthy male Sprague-Dawley (SD) rats were randomized into normal control group, diabetic nephropathy group and diabetic nephropathy with AS-IV treatment group. DN was induced by intraperitoneal injection of streptozotocin (STZ). AS-IV treatment started 2 weeks before STZ injection and lasted 14 weeks. 24h Urinary proteins were measured 4, 8 and 12 weeks after STZ injection. Body weight, blood glucose, blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured 12 weeks after STZ injection. Renal pathology, podocyte morphological changes, podocyte density, protein and mRNA expression of integrin α3, integrin β1 and integrin-linked kinase (ILK) were detected by histopathology, electron microscopy, immunohistochemistry, western blot and real-time PCR, respectively. Hyperglycemia, proteinuria, mesangial expansion and podocyte loss, increased protein expression of ILK and decreased protein expression of integrin α3 and integrin β1 were detected in diabetic rats. AS-IV treatment ameliorated podocyte loss, renal histopathology and podocyte foot process effacement, decreased proteinuria, partially restored protein expression of integrin α3, integrin β1 and ILK. These findings suggested that AS-IV may protect podocyte and ameliorate diabetic nephropathy by inhibiting the expression of ILK and restoring the expression of integrin α3β1 in diabetic rats.
authors.affiliation: Department of Nephrology, ZheJiang Hospital, HangZhou, PR China. Electronic address: doctor_chen@126.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Nephrology, ZheJiang Hospital, HangZhou, PR China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nephrology, ZheJiang Hospital, HangZhou, PR China.
authors.forename: Yunling
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Nephrology, Shanghai Sixth People׳s Hospital, Shanghai, PR China.
authors.forename: Dingkun
authors.initials: D
authors.lastname: Gui
authors.affiliation: Institute of Integrated Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Nephrology, ZheJiang Hospital, HangZhou, PR China. Electronic address: hdy331@qq.com.
authors.forename: Dongyuan
authors.initials: D
authors.lastname: He
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D050533:Glomerular Basement Membrane / Q000502:physiology; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D050199:Podocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D000099200:Scaffold Protein ILK
chemical_list: D039422:Integrin alpha3; D019012:Integrin beta1; D020011:Protective Agents; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012503:Saponins; D014315:Triterpenes; D000099200:Scaffold Protein ILK; C052064:astragaloside A
keywords: Astragaloside IV; Diabetic nephropathy; Integrin α3β1; Integrin-linked kinase; Podocyte