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目的研究可诱导共刺激分子融合蛋白(ICOSIg)对过敏性支气管哮喘(简称哮喘)小鼠的治疗作用。方法32只健康雌性BALB/c小鼠用分段随机分组法将小鼠随机分成4组。哮喘组(A组)、ICOSIg治疗组(B组)、同型抗体对照组(C组)、生理盐水气雾激发对照组(D组),每组8只,采用重组真核表达技术制备ICOSIg,建立鸡卵白蛋白(OVA)免疫小鼠哮喘模型,给予ICOSIg治疗后观察其气道阻力变化、支气管肺泡灌洗液(BALF)中细胞总数、各炎性细胞百分比及白细胞介素4(IL4)、γ干扰素(IFNγ)和总免疫球蛋白E(IgE)含量的变化;采用流式细胞仪(FACS)检测T辅助细胞(Th)亚群变化;取肺组织行病理组织学分析观察肺内炎症情况。结果(1)制备的ICOSIg可与哮喘小鼠脾脏B细胞上相应配体结合。(2)B组小鼠气道压力变化为[(33±12)%],与A组[(58±10)%]比较差异有统计学意义(P<0.01)。B组BALF中细胞总数为[(5.9±3.1)×107/L],与A组[(22.6±5.3)×107/L]比较差异有统计学意义(P<0.01);B组嗜酸粒细胞数为0.020±0.020,与A组(0.070±0.030)比较差异有统计学意义(P<0.01);B组IL4水平为(77±31)ng/L,与A组[(179±44)ng/L]比较差异有统计学意义(P<0.01);B组外周血中总IgE水平为(175±33)μg/L,与A组[(282±22)μg/L]比较差异有统计学意义(P<0.01);B组Th2细胞比例为(4.5±1.0)%,与A组[(11.1±2.5)%]比较差异有统计学意义(P<0.01)。(3)与A组比较,B组小鼠肺内炎性浸润明显减轻、上皮细胞完整、管腔内少见分泌物。结论ICOSIg可体内阻断可诱导共刺激通路、减少Th2免疫反应偏移并抑制IgE的生成,对过敏性哮喘有治疗作用。
Objective To study the therapeutic effect of inducible costimulatory molecule fusion protein (ICOSIg) on allergic bronchial asthma (asthma) mice. Methods Thirty-two healthy female BALB / c mice were randomly divided into 4 groups using the segmented randomization method. ICOSIg treatment group (group A), ICOSIg treatment group (group B), the same antibody group (group C), saline aerosol challenge control group (group D), each group of eight, using recombinant eukaryotic expression technology ICOSIg, The model of asthma induced by ovalbumin (OVA) in mice was established. The changes of airway resistance were observed after ICOSIg treatment. The total number of cells, the percentage of inflammatory cells and the levels of interleukin 4 (IL-4) in bronchoalveolar lavage fluid (BALF) (IFNγ) and total immunoglobulin E (IgE). The changes of T helper cell (Th) subsets were detected by flow cytometry (FACS), and the histopathological analysis was performed to observe the lung inflammation Happening. Results (1) The prepared ICOSIg binds to the corresponding ligand on spleen B cells of asthmatic mice. (2) The change of airway pressure in group B was [(33 ± 12)%] compared with that in group A (58 ± 10)%] (P <0.01). The total number of cells in BALF in group B was (5.9 ± 3.1) × 107 / L, which was significantly lower than that in group A (22.6 ± 5.3) × 107 / L, P <0.01) The cell number was 0.020 ± 0.020, which was significantly lower than that in group A (0.070 ± 0.030) (P <0.01) (P <0.01). The level of total IgE in peripheral blood of group B was (175 ± 33) μg / L compared with that of group A [(282 ± 22) μg / L] (P <0.01). The proportion of Th2 cells in group B was (4.5 ± 1.0)%, which was significantly different from that in group A (11.1 ± 2.5%) (P <0.01). (3) Compared with group A, inflammatory infiltration of lung in group B was significantly reduced, epithelial cells were intact, and rare secretions were found in the lumen. Conclusion ICOSIg can block the inducible co-stimulatory pathway in vivo, reduce the shift of Th2 immune response and inhibit the production of IgE, which has a therapeutic effect on allergic asthma.