RNA干扰实验性治疗类风湿关节炎小鼠模型的建立

Establishment of mice model for rheumatoid arthritis experimental treatment by RNA interference

目的为靶向TNF-α的RNA干扰实验性治疗类风湿关节炎(RA)提供合适的动物模型。方法取20只DBA/1小鼠随机分为模型组和对照组各10只,模型组分别于第1、21天自尾根部取3点皮内注射牛Ⅱ型胶原(CⅡ)与褔氏完全佐剂充分乳化的胶原乳剂100μl,对照组同上方法注射褔氏完全佐剂与0.1M冰醋酸等体积乳化液100μl。观察小鼠有无关节炎表现并进行关节炎评分;第45天,麻醉小鼠取静脉血、ELISA法检测血清TNF-α水平,处死小鼠对下肢关节进行组织病理学检查。结果模型组多于第28～32天出现关节红肿等关节炎表现、关节炎评分逐渐升高且显著,对照组无关节炎症状且关节炎评分为0;模型组和对照组血清TNF-α水平分别为(56.772±9.951)、(30.241±7.103)ng/ml,(t=6.8623,P<0.001);病理检查显示,模型组受累关节出现炎性细胞浸润、滑膜增生等。结论本文构建的CIA小鼠模型充分模拟了人类RA的特点,可用于靶向TNF-α的RNA干扰治疗RA的实验研究。

Objective To provide proper animal model for rheumatoid arthritis（RA）experimental treatment by RNA interference targeting TNF-α.Methods Twenty DBA/1 mice were divided randomly into model group and control group with 10 in each,the model group were injected intradermally at the root of the tail with 100 μl emusion containing an equal volume of bovine type Ⅱcollagen solution and complete Freund＇s adjuvant on the 1st and 21st day.The control group were given 100 μl emusion containing an equal volume of complete Freund＇s adjuvant and glacial acetic acid.The arthritis features were investigated and evaluated.The serum samples were obtained on day 45 for TNF-α examination by ELISA,and hind paws were collected for histopathology examination.Results Most of the mice in the model group characterized by joint swelling and redness on day 2832,and arthritis sores increased gradually.No above features were found in the control group.The serum TNF-α level of model group and control group were（56.772±9.951）and（30.241±7.103）ng/ml（t=6.862 3,P〈0.001）.The synovium hyperplasia and inflammation were found in the model group.Conclusion The mice model constructed in this study can simulate the characteristics of human rheumatoid arthritis,and suitable for research of RA experimental treatment by RNA interference targeting TNF-α.