论文部分内容阅读
背景:淋巴细胞异常激活以及核因子κB依赖非特异性的炎症反应是类风湿关节炎关节组织炎症损害的两个重要方面。共刺激信号CD40/CD40L是T细胞识别、活化中最重要的共刺激分子。IκBα有效的抑制核因子κB的途径,可以在中心环节上抑制炎症反应的产生,抑制炎症因子滑膜组织的损害。目的:采用CD40LIg-IRES2-IκBα双基因表达的腺病毒载体转染到关节炎动物模型,探索双基因共表达腺病毒载体转染对免疫性关节炎的治疗效果。方法:构建pA dC D40LIg-IRES2-IκBα双基因共表达腺病毒载体。采用含1 g/LⅡ型胶原蛋的完全弗氏佐剂皮下多点注射构建关节炎Wistar大鼠模型。将20只构建成功的关节炎大鼠模型分为未处理组和转染组,分别给予2组大鼠四肢末端关节腔注射生理盐水和pA d CD40LIg-IRES2-IκBα腺病毒载体。结果与结论:转染14 d后,与未处理组相比,转染组大鼠关节炎评分、关节液中淋巴细胞CD40L表达水平、关节滑膜组织中核因子κB p65表达水平、关节液内白细胞介素2、白细胞介素6、肿瘤坏死因子α、间质金属蛋白酶3和间质金属蛋白酶9的水平降低。提示共表达CD40LIg和IκBα腺病毒载体局部转染可有效抑制关节炎大鼠关节炎症状,降低关节腔内炎性细胞因子及炎性分子在滑膜组织中的表达,取得良好的治疗效果。
BACKGROUND: Abnormal lymphocyte activation and nuclear factor-κB-dependent nonspecific inflammatory responses are two important aspects of the inflammatory damage of the joint tissues of rheumatoid arthritis. Costimulatory signal CD40 / CD40L is the most important costimulatory molecule in T cell recognition and activation. IκBα can effectively inhibit the nuclear factor κB pathway, which can inhibit the production of inflammatory reaction in the central part and inhibit the damage of inflammatory factor synovial tissue. OBJECTIVE: To investigate the therapeutic effect of double gene co-expression adenovirus vector on immune arthritis in animal model of arthritis by using adenovirus vector with CD40LIg-IRES2-IκBα double gene expression. Methods: Construct pA dC D40LIg-IRES2-IκBα double gene co-expression adenovirus vector. Arthritis Wistar rat model was established by subcutaneous injection of complete Freund’s adjuvant with 1 g / L type II collagen. Twenty successful rat models of arthritis were divided into untreated group and transfection group. Two groups of rats were injected intraperitoneally with saline and pA d CD40LIg-IRES2-IκBα adenovirus vector respectively. RESULTS AND CONCLUSION: Compared with untreated group, the expression of CD40L in synovial fluid, the expression of NF-κB p65 in synovial tissue, the level of leukocyte in synovial fluid Interleukin 2, Interleukin 6, Tumor Necrosis Factor α, Intermediate Metalloproteinase 3, and Matrix Metalloproteinase 9 are reduced. Tip local co-expression of CD40LIg and IκBα adenovirus vector local transfection can effectively inhibit the arthritis of arthritis symptoms, reduce the intra-articular inflammatory cytokines and inflammatory molecules in synovial tissue expression and achieve good therapeutic effect.