Gene transfer therapy trial of Chondromodulin I for the experimental arthritis

在刘易斯大鼠的两个足垫处注射丁酸支原体（第0天）。第<10>0、7、14和21天，在右膝关节注射AxCAChM-I（软骨调节蛋白I重组腺病毒）的1x 10 μ pfu病毒，在左膝关节注射AxCALacZ（β-半乳糖苷酶重组腺病毒）。在另一只大鼠中按照相同的方案注射PBS作为基础对照。每天观察大鼠的关节炎发作，通过对每个膝关节的严重程度和滑膜炎进行分级来获得关节炎指数，从第10天到第14天观察膝关节的关节炎。免疫组化染色显示，AxCALacZ在关节滑膜组织中呈阳性表达。免疫组化染色显示，AxCAChM-I组大鼠的肝组织无明显损伤，且与AxCALacZ组相比，AxCAChM-I组大鼠的肝组织损伤程度明显减轻。用AxCAChM-I处理的滑膜中的血管数量少于用AxCALacZ处理的。但PBS组滑膜血管数少于AxCAChM-I组。软骨调节蛋白I的基因治疗可能是治疗类风湿性关节炎的有效方法之一，但我们必须改变腺病毒载体的方法。

Lewis rats were injected at their both footpads with M.Butyricum(day 0). 1x10^<10>pfu virus of AxCAChM-I(Chondronodulin I recombinant Adenovirus) was injected in right knee joint and AxCALacZ(β-galactosidase recombinant Adenovirus) were injected in left knee joint at day 0,7,14,and 21. PBS was injected as same protocol in anther rats for basal control. Rats were observed daily for the onset of the arthritis, and an arthritic index was derived by grading the severity and synovitis of each knee joint.The arthritis of knee joint was observed from day 10 to day 14. The body weight was decreased after arthritis progression.AxCALacZ was presented in synovial tissue in injected knee joint by immnohistochemical staining. No liver injury was observed by injection into knee joint, which was also checked by immunohistochemical staining.Progression of disease was suppressed by AxCAChM-I compared with AxCALacZ injected rats. The number of blood vessels in synovium treated with AxCAChM-I was less than treated with AxCALacZ. But the number of vessels in synovium treated with PBS was less than treated with AxCAChM-I. This is caused by immunogenicity of adenovirus vector.Gene therapy with Chondronodulin I may be one of the useful methods for rheumatoid arthritis, but we have to change the adenoviral delivery methods for Chondronodulin I treatment.