脂肪间充质干细胞可调节变应性鼻炎T细胞的免疫状态  

Adipose-derived mesenchymal stem cells regulate T cell immune status in allergic rhinitis

作　　者：肖二彬[1] 赵宝建[1] 张驰[1] 

机构地区：[1]河北大学附属医院耳鼻喉科,河北省保定市071000

出　　处：《中国组织工程研究》2016年第10期1373-1381,共9页Chinese Journal of Tissue Engineering Research

摘　　要：背景:脂肪间充质干细胞是一种多能干细胞,具有自我更新和增殖潜能,并具有低免疫原性以及免疫调节优势。目的:探讨脂肪间充质干细胞对小鼠变应性鼻炎T细胞免疫状态的影响。方法:(1)将60只小鼠随机分为6组(分组表示为致敏/激发/处理):卵清蛋白/卵清蛋白/高剂量脂肪间充质干细胞组(简称高剂量脂肪间充质干细胞组)、卵清蛋白/卵清蛋白/低剂量脂肪间充质干细胞组(简称低剂量脂肪间充质干细胞组)、卵清蛋白/卵清蛋白/PBS组、卵清蛋白/卵清蛋白组/0组、PBS/PBS组/0组、正常对照组。前5组分别于第0,7,14天的相同时间腹腔注射200μL卵清蛋白致敏液或PBS进行基础致敏,第15-19天每天给予20μL卵清蛋白激发液或PBS进行激发,正常对照组不做任何处理。在致敏激发后的第20-22天,前3组分别经尾静脉注射0.1 mL的高、低浓度脂肪间充质干细胞液及PBS。(2)末次处理48 h后,采用ELISA法检测血清白细胞介素4、白细胞介素6、白细胞介素10和干扰素-γ水平,荧光定量PCR法检测脾脏上述各细胞因子m RNA的表达,荧光显微镜观察荧光标记脂肪间充质干细胞在鼻黏膜的迁移情况,苏木精-伊红染色观察鼻黏膜的病理学变化。结果与结论:(1)高剂量脂肪间充质干细胞组与卵清蛋白/卵清蛋白组相比,血清和脾脏白细胞介素4和白细胞介素6水平显著下降(P<0.05),白细胞介素10和干扰素-γ水平显著增加(P<0.05)。(2)低剂量脂肪间充质干细胞组与卵清蛋白/卵清蛋白组比较,血清和脾脏中白细胞介素6水平显著下降(P<0.05),白细胞介素10水平显著增加(P<0.05),白细胞介素4和干扰素-γ的水平无显著性变化(P>0.05)。(3)荧光标记的脂肪间充质干细胞可向鼻黏膜迁移分布,高浓度脂肪间充质干细胞组明显多于低浓度脂肪间充质干细胞组。(4)高、低浓度脂肪间充质干细胞组鼻黏膜中嗜酸性粒细胞浸润明显减轻。(5)脂�BACKGROUND： Adipose-derived mesenchymal stem cells are a kind of pluripotent stem cells that have the potential of self-renewal and proliferation, and have low immunogenicity and immunomodulatory role. OBJECTIVE： To study the effects of adipose-derived mesenchymal stem cells on T cell immune status of allergic rhinitis mouse models. METHODS： Sixty mice were randomly assigned into six groups（sensitized/challenged/treatment）： experimental group 1 was given ovalbumin/ovalbumin/high-dose adipose-derived mesenchymal stem cells, experimental group 2 given ovalbumin/ovalbumin/low-dose adipose-derived mesenchymal stem cells, experimental group 3 given ovalbumin/ovalbumin/PBS, experimental group 4 given ovalbumin/ovalbumin/0, and experimental group 5 given PBS/PBS/0, and normal control group given no treatment. In the former five groups, intraperitoneal injection of 200 μL ovalbumin sensitizing solution or PBS was conducted for basic sensitization at days 0, 7, 14; 20 μL ovalbumin challenging solution or PBS was given for challenging at days 15-19. In the former three groups, 0.1 m L of high-dose, low-dose adipose-derived mesenchymal stem cells or PBS was given via the tail vein, respectively, at days 20-22 after sensitization and challenge. At 48 hours after final treatment, ELISA was used to detect serum levels of interleukin-4, interleukin-6, interleukin-10 and interferon-γ, and fluorogenic quantitative PCR used to detect the mR NA expressions of these cytokines in the spleen. Migration of fluorescent-labeled adipose-derived mesenchymal stem cells in the nasal mucosa was observed under fluorescence microscope, and pathological changes of the nasal mucosa were observed through hematoxylin-eosin staining. RESULTS AND CONCLUSION： Compared with the experimental group 4, the levels of interleukin-4 and interleukin-6 in the serum and spleen were significantly lower in the experimental group 1（P〈0.05）, and the levels of interluekin-10 and interferon-γ levels were significantly increased（P〈0.05）;

关 键 词：干细胞 脂肪干细胞 变应性鼻炎 脂肪间充质干细胞 调节性T细胞 Th1/Th2免疫平衡 

分 类 号：R394.2[医药卫生—医学遗传学]