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[建立肾虚证类风湿关节炎大鼠模型]

[Establishment of a rat model of rheumatoid arthritis with kidney deficiency syndrome].

作者信息

Wang Yan, Zhao Hong-yan, Liu Mei-jie, Xiao Cheng, Lü Cheng, Tan Yong, Zha Qing-lin, Li Yan, Liu Hong, Lü Ai-ping, Ju Da-hong

机构信息

Department of Pathology, Civil Aviation General Hospital, Beijing, China.

出版信息

Zhong Xi Yi Jie He Xue Bao. 2011 Sep;9(9):973-82. doi: 10.3736/jcim20110908.

Abstract

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.

摘要

目的

建立肾虚证类风湿关节炎(RA)大鼠模型。

方法

将110只6周龄的无特定病原体的雄性和雌性斯普拉格-道利大鼠随机分为正常对照组、假手术组、胶原诱导性关节炎(CIA)对照组、去势加CIA组和羟基脲加CIA组。去势加CIA组大鼠分别切除睾丸或卵巢。羟基脲加CIA组大鼠通过灌胃给予375 mg/(kg·d)羟基脲,连续17天。然后,CIA对照组、去势加CIA组和羟基脲加CIA组大鼠皮下注射Ⅱ型胶原与不完全弗氏佐剂的混合物以诱导类风湿关节炎。观察大鼠的一般状态、关节炎指数和关节肿胀情况以评估CIA的发病情况。采用酶联免疫吸附测定法检测血浆中抗Ⅱ型胶原抗体、白细胞介素-6(IL-6)、IL-10、干扰素-γ(IFN-γ)和皮质酮(CORT)的含量,采用放射免疫测定法检测肾上腺环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)水平。

结果

与CIA对照组相比,肾虚CIA大鼠(去势加CIA组和羟基脲加CIA组)关节肿胀和关节损伤程度明显增加,出现类似于人类临床症状的肾虚证,如精神萎靡、弓背、迟钝、饮食减少和肛周污染;这两组大鼠的cAMP/cGMP比值明显降低;雄性大鼠CORT含量升高,雌性大鼠降低,抗Ⅱ型胶原抗体含量明显升高;去势加CIA组中IFN-γ、IL-6和IL-10的含量明显升高。

结论

肾虚证RA大鼠模型既有明显的肾虚证又有RA的特征,能反映部分患者特点。然而,去势更适合诱导大鼠肾虚证RA。

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