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Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (9): 973-982.doi: 10.3736/jcim20110908

• Original Experimental Research • Previous Articles     Next Articles

Establishment of a rat model of rheumatoid arthritis with kidney deficiency syndrome

Yan Wang1, Hong-yan Zhao2, Mei-jie Liu2, Cheng Xiao3, Cheng Lü4, Yong Tan4, Qing-lin Zha5, Yan Li2, Hong Liu2, Ai-ping Lü4(), Da-hong Ju2()   

  1. 1. Department of Pathology, Civil Aviation General Hospital, Beijing 100123, China
    2. Institute of Basic Theory of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
    3. Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China
    4. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
    5. Data Analysis Center, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, Jiangxi Province, China
  • Received:2011-04-20 Accepted:2011-05-09 Online:2011-09-20 Published:2011-09-15
  • Contact: Lii Ai-ping,Ju Da-hong E-mail:lap64067611@126.com;judahong@sohu.com

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Objective: To establish a rat model of rheumatoid arthritis (RA) with kidney deficiency syndrome.

Methods: A total of 110 six-week-old specific pathogen-free male and female Sprague-Dawley rats were randomly divided into normal control group, sham-operated group, collagen-induced arthritis (CIA) control group, castration plus CIA group and hydroxyurea plus CIA group. Testiculus or ovary of rats in the castration plus CIA group was cut off, respectively. Rats in the hydroxyurea plus CIA group were given 375 mg/(kg·d) hydroxyurea by gavage administration for 17 d. Then rats in the CIA control group, castration plus CIA group and hydroxyurea plus CIA group were subcutaneously injected with mixture of type Ⅱ collagen and incomplete Freund’s adjuvant to induce rheumatoid arthritis. General state, arthritis index and joint swelling of the rats were observed to evaluate the onset of CIA. Contents of anti-type Ⅱ collagen antibody, interleukin-6 (IL-6), IL-10, interferon-γ (IFN-γ) and corticosterone (CORT) in plasma were detected by enzyme-linked immunosorbent assay, and adrenal cyclic adenylic acid (cAMP) and cyclic guanylic acid (cGMP) levels were detected by radioimmunoassay.

Results: Compared with the CIA control group, the degrees of joint swelling and joint damage were significantly increased in the kidney-deficiency CIA rats (castration plus CIA group and hydroxyurea plus CIA group), with kidney deficiency syndrome similar to human clinical symptoms, such as depressed, bowed back, dullness, reduced diet and perianal contamination; the rats in those two groups were noted with a significantly decreased ratio of cAMP/cGMP; the content of CORT was increased in male rats while decreased in female rats, with an obvious increase in the content of anti-type Ⅱ collagen antibody; the contents of IFN-γ, IL-6 and IL-10 were obviously increased in the castration plus CIA group.

Conclusion: The rat model of RA with kidney deficiency syndrome has both obvious kidney deficiency syndrome and characteristics of RA and can reflect part of the patient’s characteristics. However, castration is more suitable for inducing RA with kidney deficiency syndrome in rats.

Key words: rheumatoid arthritis, disease-syndrome combination model, kidney deficiency syndrome, rats

Figure 1

Edema rate of ankle**P<0.01, vs normal control group; △P<0.05, △△P<0.01, vs CIA control group. Data were represented as $\overline{x}$±s, n=10. CIA: collagen-induced arthritis."

Figure 2

Pathological scores of ankle and knee **P<0.01, vs normal control group; △P<0.05, △△P<0.01, vs CIA control group. Data were represented as $\overline{x}$±s, n=10. CIA: collagen-induced arthritis."

Figure 3

Level of anti-type Ⅱ collagen antibody in plasma"

Figure 4

Level of IL-6 in plasma**P<0.01, vs normal control group; △△P<0.01, vs CIA control group. Data were represented as $\overline{x}$±s, n=10. CIA: collagen-induced arthritis; IL-6: interleukin-6."

Figure 5

Level of IL-10 in plasma **P<0.01, vs normal control group; △△P<0.01, vs CIA control group. Data were represented as $\overline{x}$±s, n=10. CIA: collagen-induced arthritis; IL-10: interleukin-10."

Figure 6

Level of IFN-γ in plasma**P<0.01, vs normal control group; △△P<0.01, vs CIA control group; ▲P<0.05, vs hydroxyurea+CIA group. Data were represented as $\overline{x}$±s, n=10. CIA: collagen-induced arthritis; IFN-γ: interferon-γ."

Figure 7

Level of CORT in plasma **P<0.01, vs normal control group; △P<0.05, △△P<0.01, vs CIA control group; ▲▲P<0.01, vs hydroxyurea+CIA group. Data were represented as $\overline{x}$±s, n=10. CIA: collagen-induced arthritis; CORT: corticosterone."

Figure 8

Levels of cAMP and cGMP in adrenal glands and the radio of cAMP to cGMP*P<0.05, **P<0.01, vs normal control group; △P<0.05, △△P<0.01, vs CIA control group. Data were represented as $\overline{x}$±s, n=10. CIA: collagen-induced arthritis; cAMP: cyclic adenylic acid; cGMP: cyclic guanylic acid."

Figure 9

Levels of cAMP and cGMP in adrenal glands and the radio of cAMP to cGMP*P<0.05, **P<0.01, vs normal control group; △P<0.05, △△P<0.01, vs CIA control group. Data were represented as $\overline{x}$±s, n=10. CIA: collagen-induced arthritis; cAMP: cyclic adenylic acid; cGMP: cyclic guanylic acid."

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