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Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (2): 186-193.doi: 10.3736/jcim20110212

• Original Experimental Research • Previous Articles     Next Articles

Anti-angiogenic effects of genistein on synovium in a rat model of type Ⅱ collagen-induced arthritis

Jin-xin Xu1, Yu Zhang1(), Xue-zeng Zhang2, Ying-ying Ma1   

  1. 1. Department of Hematopathy and Rheumatism, Clinical Medicine College, Yangzhou University, Yangzhou 225001, Jiangsu Province, China
    2. Qingdao Health School, Qingdao 266071, Shandong Province, China
  • Received:2010-11-11 Accepted:2010-12-17 Online:2011-02-20 Published:2011-02-15
  • Contact: Zhang Yu E-mail:yzzy10182001@yahoo.com.cn

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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.
Conclusion: 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.

Key words: rheumatoid arthritis, genistein, arthritis, experimental, vascular endothelial growth factor, angiogenesis, matrix metalloproteinases, synovial membrane, rats

Figure 1

Arthritis index score of rats"

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Figure 2

Paw volume of rats in different groups"

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Figure 3

CD31-labeled microvessels in synovial tissue of rats observed by immunohistochemiscal method (Light microscopy, ×200) A: Normal group; B: Model group; C: Methotrexate group; D: Genistein group; E: Genistein plus methotrexate group. The pictures showed the numbers of microvessels in synovial tissues of the five groups. There were only two microvessels in the normal group, and the number of microvessels in the model group was the most. The number of microvessels in each treatment group was less than that in the model group, and the number of microvessels in the genistein plus methotrexate group was the least."

Figure 4

Microvessel density in synovial tissue of rats in different groups *P<0.05, vs normal group; △P<0.05, vs model group; ▲P<0.05, vs Gen+MTX group. Data were represented as x±s, n=8. Rats in each group were treated with normal saline (control and model group), 30 mg/（kg·d） genistein (Gen group), methotrexate at 0.2 mg/kg body weight (MTX group) or genistein plus methotrexate (Gen+MTX group) respectively for 6 weeks. After treatment, the synovial tissues were collected and observed by immunohistochemiscal method."

Figure 5

Serum levels of vascular endothelial growth factor and matrix metallopeptidase-1, 2 and 9 proteins of rats observed by Western blotting Ⅰ: Normal group; Ⅱ: Model group; Ⅲ: Gen group; Ⅳ: MTX group; Ⅴ: Gen+MTX group. *P<0.05, vs normal group; △P<0.05, vs model group; ▲P<0.05, vs Gen+MTX group. Data were represented as x±s, n=8. Rats in each group were treated with normal saline (control and model group), 30 mg/（kg·d） genistein (Gen group), methotrexate at 0.2 mg/kg body weight (MTX group) or genistein plus methotrexate (Gen+MTX group) respectively for 6 weeks. After treatment, the serum was collected and vascular endothelial growth factor and matrix metallopeptidase-1, 2 and 9 proteins in the serum were observed by Western blotting."

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