新型鸡Ⅱ型胶原基因疫苗治疗胶原诱导的大鼠类风湿性关节炎的疗效观察

目的系统观察含编码鸡Ⅱ型胶原基因（CCOL2A1）疫苗pcDNA-CCOL2A1对大鼠胶原诱导的关节炎（CIA）的治疗作用。方法以鸡Ⅱ型胶原（CCⅡ）诱导的Wistar大鼠为类风湿关节炎（RA）模型即CIA,系统观察一次性尾部静脉注射20μg/kg、200μg/kg、400μg/kg3个不同剂量pcDNA-CCOL2A1基因疫苗和pcDNA3．1空载体对CIA的治疗效果。通过评估治疗前后CIA鼠关节肿胀指数的改善,结合放射影像学和组织病理学方法,系统分析pcDNA-CCOL2A1基因疫苗对CIA关节炎的治疗作用。结果CIA大鼠在注射pcDNA-CCOL2A1基因疫苗后的第5天,在200μg/kg剂量组就可观察到CIA大鼠四肢关节肿胀程度明显减轻;放射影像学和组织病理学检查显示,经过200μg/kg治疗后,使关节软骨及其下面的骨小梁结构与正常组接近,关节软骨及其下面的骨质结构得到保护,可使炎症分数下降为对照组的50％,仅关节滑膜略有增生,与空载体组比较差异有统计学意义（P〈0．05）;而20μg/kg和400μg/kg两剂量组与空载体组比较则无任何治疗效果（P〉0．05）。结论pcDNA-CCOL2A1基因疫苗对CIA大鼠关节炎有显著的治疗作用。

Therapeutic effect of a novel recombinant vaccine encoding chicken collagen type II procollagen gene on collagen-induced arthritis in rat

OBJECTIVE: To investigate the therapeutic effect of gene vaccine encoding chicken collagen type II (CC II) on collagen-induced arthritis (CIA) comprehensively. METHODS: Three groups (CIA) were given a single intravenous injection of plasmid pcDNA-CCOL2A1 (20 microg/kg, 200 microg/kg, 400 microg/kg) respectively and one group (CIA) was injected 200 microg/kg pcDNA3.1 as a control. The effect of gene vaccine (pcDNA-CCOL2A1) was evaluated according to the arthritis score, radiological and histological examinations. RESULTS: The severity of arthritis of CIA rats which were administered 200 microg/kg pcDNA-CCOL2A1 was significantly reduced from the fifth day. According to the radiological and histological examinations, the articular cartilage as well as subchondral bone trabeculae are similar to those of the normal groups, so the bone and articular cartilage structure were protected after treatment with 200 microg/kg pcDNA-CCOL2A1 with a little synovial hyperplasia. The therapeutic effect of 200 microg/kg pcDNA-CCOL2A1 group has significant difference in comparison with that of the pcDNA3.1 group (P < 0.05) and the arthritis scores are reduced to about 50% of those in control groups, but 20 microg/kg group and 400 microg/kg group has no therapeutic effect in our observation (P > 0.05). CONCLUSION: The new gene vaccine pcDNA-CCOL2A1 has significant therapeutic effect on CIA rats, and the treatment may therefore be an effective strategy for RA patient clinically.