title: [Anti-angiogenic effects of genistein on synovium in a rat model of type II collagen-induced arthritis].
abstract: OBJECTIVE
  To explore the anti-angiogenic effects of genistein on synovium in a rat model of type II collagen-induced arthritis (CIA).
  
  
  METHODS
  Forty SD rats were randomly divided into normal group, model group, genistein group, methotrexate (MTX) group and Gen plus MTX group with 8 rats in each group. Arthritis in rats was induced by subcutaneous injection of type II collagen combined with complete Freund's adjuvant (CFA). On the second day after the injection, 1 mL of suspension liquid of genistein (30 mg/kg body weight, once daily) and MTX (0.2 mg/kg body weight, once a week) were administered by oral gavage respectively. The rats in normal group and model group were administered with normal saline in the same volume. Synovium of knee joints and peripheral serum were collected from the CIA rats. Microvessel density in synovium (MVD) was detected by immunohistochemical method and serum vascular endothelial growth factor (VEGF) and matrix metallopeptidase (MMP)-1, 2 and 9 levels were detected by using Western blotting.
  
  
  RESULTS
  Arthritis index score, paw volume of rats in the model group were significantly higher than those in the normal group (P<0.05), which suggested that a model of CIA induced by injection of type II collagen and CFA was successfully constructed. The arthritis index scores of rats in the treatment groups were decreased compared with the model group. The results of Western blotting showed that genistein obviously attenuate the levels of VEGF and MMP-1, 2 and 9 in serum (P<0.05). Immunohistochemical method showed that MVDs in the treatment groups were reduced as compared with the model group.
  
  
  CONCLUSIONS
  The expressions of VEGF and MMP-1, 2 and 9 are related to the synovial pannus formation in CIA rats. The anti-angiogenic activity of genistein may correlate to its inhibitory effect on the expressions of VEGF and MMP-1, 2 and 9 in serum of CIA rats; genistein plus MTX are superior to single agents in treating rheumatoid arthritis.
authors.affiliation: Department of Hematopathy and Rheumatism, Clinical Medicine College, Yangzhou University, Yangzhou 225001, Jiangsu Province, China.
authors.forename: Jin-xin
authors.initials: JX
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xue-zeng
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: Ma
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000473:pathology*; D024043:Collagen Type II / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D024043:Collagen Type II; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D019833:Genistein; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1