| 摘要: |
| 目的 利用完全弗氏佐剂（CFA）建立雌性SD大鼠类风湿关节炎（RA）模型，并考察不同给药方式的塞来昔布对RA的治疗效果。方法 将24只雌性SD大鼠随机分成正常对照组和低、中、高剂量模型组（n=6），低、中、高剂量模型组分别用0.05、0.1、0.2 mL CFA（10 mg/mL）于大鼠右后肢足跖部注射诱导构建RA模型，筛选出合适的剂量。另取24只雌性SD大鼠分为正常对照组、模型对照组、塞来昔布口服组、塞来昔布注射组（n=6），后3组利用最佳致炎剂量CFA建立RA模型。塞来昔布口服组给予市售塞来昔布胶囊，每天灌胃1次，每次20 mg；塞来昔布注射组给予用原料药配制的塞来昔布混悬液，每周于大鼠右后肢足跖部注射给药1次，剂量20 mg/kg。测量各组大鼠足容积，并进行临床评分。通过ELISA检测各组大鼠血清中3种炎症因子（IL-1β、IL-6、TNF-α）的浓度，取大鼠踝关节组织进行H-E染色以观察组织病变情况。结果 在雌性SD大鼠中，足跖部注射0.1 mLCFA（10 mg/mL）可较好地模拟RA中度炎症反应，注射CFA后逐渐出现足爪红肿，全身临床评分及足部关节炎指数评分均有升高，炎症高峰期在免疫后19 d。塞来昔布口服组和注射组足容积较模型对照组减小（P均<0.05），全身临床评分及足部关节炎指数评分均较模型对照组降低（P均<0.01），血清IL-1β、IL-6、TNF-α浓度均较模型对照组降低（P均<0.05），踝关节组织病理改变均较模型对照组减轻；其中塞来昔布注射组的全身临床评分及足部关节炎指数评分低于口服组（P均<0.05），踝关节组织病理改变轻于口服组。结论 足跖部注射0.1 mL CFA（10 mg/mL）可致SD雌性大鼠中度炎症反应，能较好地模拟RA的病理过程。每周经足跖部注射1次塞来昔布混悬液对模型大鼠RA的疗效优于每天口服1次塞来昔布。 |
| 关键词: 类风湿关节炎 雌性大鼠模型 完全弗氏佐剂 塞来昔布 给药方式 |
| DOI：10.16781/j.CN31-2187/R.20190308 |
| 投稿时间：2019-03-31修订日期：2020-04-07 |
| 基金项目:国家自然科学基金（81690264，81821004）. |
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| Establishment of rheumatoid arthritis model in female SD rats with complete Freund's adjuvant and the therapeutic effects of celecoxib |
| SUN Rui-meng,YANG Bai-xue,GONG Yan-chang,HAO Jing-qiang,SUN Hao-wei,LI San-ming* |
(School of Pharmacy, Shenyang Pharmaceutical University, Benxi 117004, Liaoning, China
*Corresponding author) |
| Abstract: |
| Objective To construct a rheumatoid arthritis (RA) model of female SD rats with complete Freund's adjuvant (CFA), and to investigate the therapeutic effects of celecoxib on RA with different administration methods. Methods Twenty-four female SD rats were randomly divided into normal control group and low-, medium-, high-dose model groups (n=6), and 0.05, 0.1 and 0.2 mL of CFA (10 mg/mL) were injected into the right hind limb plantar region of the rats to induce RA models, and the appropriate dose was screened. Another 24 female SD rats were randomly divided into normal control group and 3 experimental groups after the establishment of the optimal inflammation model (model control group, celecoxib oral group, and celecoxib injection group) (n=6). The celecoxib oral group was given commercial celecoxib capsules, 20 mg each time, once a day by gavage; the celecoxib injection group was given a celecoxib suspension, administered once a week at a dose of 20 mg/kg. The foot volume of rats was measured in each group, and the clinical scores were performed. The levels of 3 inflammatory factors (interleukin[IL]-1β, IL-6, and tumor necrosis factor α[TNF-α]) in serum of rats in each group were detected by enzyme-linked immunosorbent assay, and the ankle joint tissues of rats were stained with hematoxylin-eosin staining to observe the pathological changes. Results In female SD rats, moderate inflammatory reaction of RA could be better simulated by injecting 0.1 mL CFA (10 mg/mL) into the plantar part of the foot. After CFA injection, the feet gradually become red and swollen, and the systemic clinical score and foot arthritis index score were both increased. The peak of inflammation appeared on day 19 after immunization. The foot volume, systemic clinical score, foot arthritis index score, the concentrations of serum IL-1β, IL-6 and TNF-α of the rats in the celecoxib oral group and injection group were significantly lower than those in the model control group (all P<0.05), and the pathological changes of ankle joint were all alleviated. The systemic clinical score and foot arthritis index score of the rats in the celecoxib injection group were significantly lower than those in the oral group (both P<0.05), and the pathological changes of ankle joint were mild in the injection group. Conclusion Injection of 0.1 mL CFA (10 mg/mL) into the plantar region of the foot can cause moderate inflammation reaction in female SD rats, and it can better simulate the pathological process of RA. Injecting celecoxib suspension once a week has a better effect than taking celecoxib orally once a day on RA in model rats. |
| Key words: rheumatoid arthritis female rat model complete Freund's adjuvant celecoxib mode of administration |
