目的 探讨在致敏前和致敏后脂肪间充质干细胞 （ADSC）腹腔注射移植对Balb/c小鼠食物过敏的免疫干预作用。方法 将32只3周龄Balb/c雌性小鼠随机分为空白对照组、过敏模型组、ADSC治疗组和ADSC预防组，每组8只。利用卵清蛋白 （OVA）腹腔注射致敏建立小鼠食物过敏模型，ADSC预防组和治疗组分别在造模第1天和第15天进行干细胞移植 （1×106个细胞数）。观察各组小鼠相关的过敏症状并进行评分；苏木精-伊红染色观察各组小鼠空肠绒毛及炎性细胞浸润情况；采用Luminex液相芯片技术检测各组小鼠血清中过敏相关的细胞因子水平变化。结果 与过敏模型组相比，ADSC治疗组和预防组过敏症状评分均明显降低 （P<0.05），同时这两组的空肠黏膜过敏性病理损伤显著减轻。与过敏模型组比较，ADSC预防组和治疗组IL-4、IL-5、IL-6、IL-17A、IL-22、IL-23水平显著下降 （P<0.05）。与过敏模型组和ADSC预防组比较，ADSC治疗组IFN-γ水平升高，MCP-1水平下降 （P<0.05）。结论 ADSC移植对致敏前或致敏后的Balb/c幼鼠食物过敏均有免疫干预作用，致敏后ADSC移植比致敏前移植免疫调节效果更好。
Abstract
Objective To investigate the immunoregulatory effect of adipose-derived stem cell (ADSC) transplantation by intraperitoneal injection in food-allergic young mice before and after ovalbumin (OVA) sensitization. Methods Thirty-two 3-week-old female Balb/c mice were randomly divided into control, allergic model, ADSC treatment, and ADSC prevention groups (n=8 each). A young mouse model of food allergy was established by OVA sensitization via intraperitoneal injection. Each mouse from the prevention and treatment groups was transplanted with 1×106 ADSCs on days 1 and 15 post-sensitization, respectively. The allergic symptoms of all groups were observed and scored. The jejunal villi and inflammatory cell infiltration were observed by hematoxylin-eosin staining. Serum levels of allergy-related inflammatory cytokines were measured by Luminex. Results Compared with the allergic model group, the ADSC prevention and ADSC treatment groups had significantly reduced allergic symptom scores (P<0.05). The two groups also showed significantly alleviated allergic pathological damage of the jejunal mucosa. Serum levels of interleukin (IL)-4, IL-5, IL-6, IL-17A, IL-22 and IL-23 were significantly lower in the ADSC prevention and treatment groups than in the allergic model group (P<0.05). However, the ADSC treatment group had a significantly increased serum interferon-γ level and a significantly reduced serum monocyte chemotactic protein-1 level compared with the allergic model and ADSC prevention groups (P<0.05). Conclusions ADSC transplantation, performed before or after sensitization, has an immunoregulatory effect on food allergy in young Balb/c mice, but this effect is better if transplantation is performed after sensitization.
关键词
食物过敏 /
脂肪间充质干细胞 /
免疫调节作用 /
卵清蛋白 /
小鼠
Key words
Food allergy /
Adipose-derived stem cell /
Immunoregulatory effect /
Ovalbumin /
Mice
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参考文献
[1] 张雅蓉, 陈云, 赵艾, 等. 中国3~12 岁儿童自报食物过敏与食物不耐受的相关因素分析[J]. 卫生研究, 2015, 44(2): 226- 231.
[2] 黄娟, 黄东明, 肖晓雄, 等. 2010 年中山市城区0~14 岁儿童哮喘流行病学调查[J]. 中国当代儿科杂志, 2015, 17(2): 149- 154.
[3] Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies[J]. Tissue Eng, 2001, 7(2): 211-228.
[4] Abreu SC, Antunes MA, Maron-Gutierrez T, et al. Bone marrow mononuclear cell therapy in experimental allergic asthma: Intratracheal versus intravenous administration[J]. Respir Physiol Neurobiol, 2013, 185(3): 615-624.
[5] Cho KS, Park HK, Park HY, et al. IFATS collection: Immunomodulatory effects of adipose tissue-derived stem cells in an allergic rhinitis mouse model[J]. Stem Cells, 2009, 27(1): 259-265.
[6] 李冠雪. 脂肪来源间充质干细胞(ADSC) 调控变应性鼻炎模型鼠T 细胞免疫状态的研究[D]. 广州: 南方医科大学, 2013.
[7] 王本贞, 郑成中. CPG 寡核苷酸对卵清蛋白致敏幼鼠血清 Th1/Th2 细胞因子及肥大细胞趋化蛋白1 的影响[J]. 解放军医学院学报, 2015, 36(5): 505-509.
[8] Shin HS, Bae MJ, Jung SY, et al. Preventive effects of skullcap (Scutellaria baicalensis) extract in a mouse model of food allergy[J]. J Ethnopharmacol, 2014, 153(3): 667-673.
[9] Mosmann TR, Cherwinski H, Bond MW, et al. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. 1986[J]. J Immunol, 2005, 175(1): 5-14.
[10] 宋云熙, 曾雪峰, 夏俊波, 等. 大剂量过敏原诱导哮喘小鼠T 细胞不反应性及机制研究[J]. 免疫学杂志, 2007, 23(3): 274- 276.
[11] van de Veerdonk FL, Netea MG. T-cell subsets and antifungal host defenses[J]. Curr Fungal Infect Rep, 2010, 4(4): 238-243.
[12] Bi Y, Liu G, Yang R. Reciprocal modulation between TH17 and other helper T cell lineages[J]. J Cell Physiol, 2011, 226(1): 8-13.
[13] 赵令. Th22 细胞及其功能分子IL-22 在系统性自身免疫病中作用的研究[D]. 长春: 吉林大学, 2013.
[14] Dhuban KB, d'Hennezel E, Ben-Shoshan M, et al. Altered T helper 17 responses in children with food allergy[J]. Int Arch Allergy Immunol, 2013, 162(4): 318-322.
[15] 曹茵茵, 冯学斌, 王跃嗣, 等. 哮喘大鼠淋巴液和血液中 Th17 细胞百分率升高及IL-23、IL-17 的表达增加[J]. 细胞与分子免疫学杂志, 2013, 29(12): 1281-1287.
[16] Pawankar R, Hayashi M, Yamanishi S, et al. The paradigm of cytokine networks in allergic airway inflammation[J]. Curr Opin Allergy Clin Immunol, 2015, 15(1): 41-48.
[17] Zhu J, Cao Y, Li K, et al. Increased expression of aryl hydrocarbon receptor and interleukin 22 in patients with allergic asthma[J]. Asian Pac J Allergy Immunol, 2011, 29(3): 266-272.
[18] Besnard AG, Sabat R, Dumoutier L, et al. Dual role of IL-22 in allergic airway inflammation and its cross-talk with IL-17A[J]. Am J Respir Crit Care Med, 2011, 183(9): 1153-1163.
[19] Taube C, Tertilt C, Gyülveszi G, et al. IL-22 is produced by innate lymphoid cells and limits inflammation in allergic airway disease[J]. PLoS One, 2011, 6(7): e21799.
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