title: Therapeutic mechanism of Saikosaponin-d in anti-Thy1 mAb 1-22-3-induced rat model of glomerulonephritis.
abstract: OBJECTIVE
  Mesangioproliferative glomerulonephritis is a common kidney disease and at present, there is no effective treatment. Our previous studies have demonstrated that Sairei-to can significantly prevent progression of experimental glomerulonephritis in rats. Although we have reported that the active component of Sairei-to in treatment of glomerulonephritis was Saikosaponin-d (Ssd), mechanism of Ssd in prevention of mesangioproliferative glomerulonephritis progression is still unknown. Therefore, current study examines the effects of Ssd on progression of mesangioproliferative glomerulonephritis induced by anti-Thy1 monoclonal antibody 1-22-3 (mAb 1-22-3) in uninephrectomized rats.
  
  
  METHODS
  Eighteen female Wistar rats first received uninephrectomy and mAb 1-22-3 injection and were then divided into 3 groups: treated daily with phosphate-buffered saline (PBS), 0.6 or 1.8 mg/kg of Ssd. Urinary protein concentration and systolic blood pressure were evaluated and the kidneys were collected and subjected to histological and immunohistological evaluation. The mRNA and protein of the kidneys were extracted and subjected to reverse transcriptase polymerase chain reaction and Western blot analysis, respectively.
  
  
  RESULTS
  Ssd reduced the amount of urinary protein and systolic blood pressure. Ssd administration also decreased extracellular matrix expansion, crescentic formation as well as infiltration of macrophages and CD8+ T lymphocytes. Moreover, Ssd significantly reduced expression of transforming growth factor beta 1 (TGF-beta1) and type I collagen in the kidneys.
  
  
  CONCLUSIONS
  Ssd inhibits the progression of mesangioproliferative glomerulonephritis through reduction of the expression of TGF-beta1 and the infiltration of macrophages and CD8+ T lymphocytes.
authors.affiliation: Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China. llucky@public3.bta.net.cn
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Gong
authors.forename: Ning
authors.initials: N
authors.lastname: Zu
authors.forename: Yajun
authors.initials: Y
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Fujio
authors.initials: F
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D024042:Collagen Type I / Q000032:analysis / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000503:physiopathology; D007518:Isoantibodies; D007678:Kidney Glomerulus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D050527:Mesangial Cells / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011507:Proteinuria / Q000188:drug therapy / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D053773:Transforming Growth Factor beta1
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D024042:Collagen Type I; D007518:Isoantibodies; D012333:RNA, Messenger; D012503:Saponins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C035678:anti-Thy antibody; D009828:Oleanolic Acid; C025759:saikosaponin D