【摘要】 目的:研究新型免疫抑制剂霉酚酸酯对哮喘小鼠骨髓CD34+造血细胞生物活性的影响,并与糖皮质激素比较,探讨其潜在的治疗哮喘的机制及可能性。方法:以卵白蛋白(OVA)致敏并激发BALB/c小鼠建立哮喘模型。连续激发2周期间分为3组,每组6只,分别给予生理盐水(对照,A组)、泼尼松(B组)及霉酚酸酯(C组)灌胃,末次激发后24h分别取支气管肺泡灌洗液(BALF)、外周血及骨髓,测定BALF、外周血中有核细胞的分类计数及骨髓中有核细胞总数;ELISA方法测定外周血中IL-5水平;流式细胞仪测定外周血及骨髓中CD34+造血细胞、CD4+T淋巴细胞占有核细胞的比例;免疫组化结合原位杂交法检测骨髓内表达白细胞介素5(IL-5)受体α链mRNA的CD34+造血细胞(CD34+IL-5RαmRNA+细胞)计数。结果:B、C组哮喘小鼠BALF中细胞总数、EOS计数、外周血中CD34+造血细胞计数及外周血中IL-5水平均低于A组相应指标,且差异有显著性(均P<0.05);C组BALF及外周血中EOS计数、骨髓中CD34+造血细胞计数及CD34+IL-5RαmRNA+细胞计数与B组相应指标比较,差异有显著性(均P<0.05)。结论:霉酚酯酸(MMF)可能抑制嗜酸粒细胞(EOS)、T淋巴细胞的肺内浸润,抑制CD34+造血细胞从骨髓迁移至外周血,它可能主要通过抑制淋巴细胞增殖,减少IL-5的产生,来影响骨髓EOS祖细胞的分化。更多还原

【Abstract】 Objective:To study the effects of mycophenolate mofetil(MMF), a new immunosuppressant, on the bioactivity of CD34+ hematopoietic cells in bone marrow of asthmatic mice, and to explore the potential antiasthmatic mechanisms by comparison with glucocorticoid. Methods: Eighteen BALB/c mice were sensitized and challenged by ovalbumin (OVA) to establish asthmatic model. Asthmatic mice were challenged by 1% OVA and divided into 3 groups fed by sterile saline (group A), prednisone (group B) and MMF (group C) respectively for two consecutive weeks. The mice were killed at 24 h after the last challenge, then bronchoalveolar lavage fluid (BALF), peripheral blood and bone marrow were prepared. Eosinophils(EOS) in peripheral blood and BALF, nucleate cells in BALF, peripheral blood and bone marrow were counted. The level of IL-5 was detected by ELISA. The percentage of CD34+cells, CD4+ T lymphocyte to nucleate cells in peripheral blood and bone marrow were counted by flow cytometry. Immunocytochemistry and in situ hybridization were employed to detect the cells expressing CD34+ and IL-5Rα mRNA (CD34+ IL-5Rα mRNA+ cells) in bone marrow. Results: There were significant differences between group B,C and group A in the total nuclear cells, the number of EOS in BALF, the number of CD34+ cells and in the level of IL-5 in peripheral blood (P < 0.05, respectively).There were significant differences between group B and group C in the number of EOS in BALF and peripheral blood, the number of CD34+ hematopoietic cells and CD34+ IL-5Rα mRNA+ cells in bone marrow(P < 0.05, respectively). Conclusion: MMF probably inhibites infiltration of eosinophils and T cells into lungs, inhibites emigration of CD34+ cells from bone marrow to peripheral blood in murine asthma model by decreasing the level of IL-5.更多还原