骨髓间充质干细胞培养上清液治疗支气管哮喘及对肺部炎症的影响

Culture supernatant of bone marrow mesenchymal stem cells for treatment of bronchial asthma and its influence on lung inflammation

背景:医学界普遍认为支气管哮喘是一种与Th2相关的免疫反应疾病,目前尚缺乏理想的治疗方法。骨髓间充质干细胞作为一种成体干细胞,不仅具有增殖和多向分化能力,还具有低免疫原性和免疫调节能力。目的:探讨骨髓间充质干细胞培养上清液对支气管哮喘小鼠肺部炎症的影响。方法:将20只实验小鼠随机分为对照组和实验组,每组10只,在第0天及第14天小鼠腹腔注射卵清蛋白溶液致敏,并在第24-26天雾化吸入卵清蛋白溶液激发。实验组从第24天开始,在每次激发前2 h,腹腔注射制备好的骨髓间充质干细胞培养上清液2 m L,对照组腹腔注射生理盐水。末次激发后麻醉致小鼠安乐死亡,采取血清、肺泡灌洗液及肺脏组织进行研究。结果与结论:1对照组小鼠肺组织结构发生异常,黏膜下层和肌层内能够看见大量嗜酸性粒细胞及单核细胞浸润,经骨髓间充质干细胞培养液治疗后,实验组小鼠肺部炎症较轻。2实验组白细胞总数、嗜酸性粒细胞数、嗜酸性粒细胞百分比显著低于对照组(P<0.01)。3实验组肺泡灌洗液以及血清中白细胞介素17水平显著低于对照组(P<0.05);肺泡灌洗液以及血清中白细胞介素4水平与对照组比较差异无显著性意义(P>0.05)。上述结果提示支气管哮喘小鼠腹腔注入骨髓间充质干细胞培养上清液能够减轻肺部炎性病理反应严重程度,降低肺泡灌洗液以及血清中相关的炎症指标水平。

BACKGROUND： Bronchial asthma is considered generally to have an association with Th2 immune response disease, but there is no ideal treatment. Bone marrow mesenchymal stem cells as a kind of adult stem cells not only have the multipotent differentiation and proliferation capacity, but also have low immunogenicity and immunoregulation ability. OBJECTIVE： To investigate the effect of culture supernatant of bone marrow mesenchymal stem cells on lung inflammation of bronchial asthma mice. METHODS： Twenty experimental mice were randomly divided into control and experimental groups, 10 mice in each group. At 0 and 14 days, intraperitoneal injection of ovalbumin induced sensitization in mice, and at 24-26 days, aerosolized ovalbumin solution was used for excitation. From the 24 th day, in the experimental group, bone marrow mesenchymal stem cell supernatant was intraperitoneally injected at 2 hours before excitation; meanwhile, normal saline was injected in the control group. At the last of excitation, the mice were sacrificed under anesthesia to take serum samples, bronchoalveolar lavage fluid and lung tissues. RESULTS AND CONCLUSION：（1） Mice in the control group appeared to have abnormal lung tissue structure, and there were a large amount of eosinophils and monocytes in the submucosa and muscularis. However, lung inflammation was relieved in the experimental group after bone marrow mesenchymal stem cell treatment.（2） The levels of interleukin-17 in the bronchoalveolar lavage fluid and serum were significantly lower in the experimental group than the control group（P〈0.05）, but there was no difference in the levels of interleukin-4 between the two groups（P〈0.05）. These findings indicate that the intraperitoneal injection of bone marrow mesenchymal stem cells can ease lung inflammation and reduce levels of inflammatory markers in the bronchoalveolar lavage fluid and serum of bronchial asthma mice.