反义uPAR质粒对AA大鼠滑膜VEGF影响的初步研究

The Primary Study of Antisense uPAR Expressing Plasmid to the VEGF in Synovial Extracellular of AA in Rats

目的:初步探讨反义uPAR质粒对在佐剂关节炎大鼠滑膜组织中血管内皮生长因子(VEGF)表达的影响。方法:40只雄性SD大鼠,其中8只为正常对照组,其余32只建立完全弗氏佐剂(CFA)诱导的大鼠AA模型,15日后将造模成功的大鼠随机分为3组,每组8只,为模型对照组、空质粒治疗组、重组质粒治疗组,后2组踝关节腔内分别注射空质粒及重组反义uPAR表达质粒,观察大鼠的一般情况、关节炎指数,关节滑膜大体变化及免疫组化法检测踝关节滑膜uPAR,VEGF的表达。结果:重组质粒治疗组关节炎指数明显低于模型对照组及空质粒治疗组(p<0.01)。uPAR和VEGF定位于滑膜组织细胞质,uPAR及VEGF表达结果,重组质粒治疗组明显低于模型对照组、空质粒治疗组(p<0.01)。反义uPAR表达质粒可以显著抑制大鼠滑膜组织uPAR、VEGF的表达。结论:反义uPAR表达质粒对AA大鼠滑膜血管翳及VEGF表达的抑制作用,可为类风湿性关节炎的基因治疗提供理论依据。

Objective：To investigate the result of antisense uPAR （urokinase-type Plasminogen Activator Receptor） expressing plasmid to the vascular endothelial growth factor （VEGF） in synovium of rats with adjuvant Arthritis. Methods： 40 male SD rats were divided into normal control group （n=8） and Adjuvant arthritis group （n=32）0. The AA rats was made by inoculating complete Freund＇s adjuvant （CFA）. After the AA model was made successfully 15 days later, The rats were randomly divided into 3 groups： 8 as model control group, 8 as vector plasmid treatment group by injecting pc DNA3.1 （-）and 8 as recombinant plasmid treatment group by injecting antisense uPAR plasmid. All the rats were selected to observe the general condition, arthritis index, the change of synovium and the expression of uPAR and VEGF detected by immunohistochemical method. Result： The expression of arthritis index （AI） were significantly lower in recombinant plasmid treatment group than in model control group and vector plasmid treatment group（P〈0.01）. The positive expression of uPAR and VEGF in synovium tissues was located incytoplasm of cell. The expression of uPAR and VEGF were significantly lower in recombinant plasmid treatment group than in model control group and vector plasmid treatment group（P〈0.01）. The antisense uPAR Expressing Plasmid could inhibit the expression of uPARand VEGF. Conclusion： The antisense uPAR Expressing Plasmid could inhibit the degradation of VEGFof AA and could provide a theory foundation for the gene treatment of RA.