Th17细胞在变应性鼻炎小鼠的表达及调控作用
发布时间：2019-03-15 08:34
【摘要】：研究目的T辅助性(Helper T, Th)细胞17是一种新的Th细胞亚型,已有研究证实它能够通过产生白介素(Interleukin,IL) 17A、IL-17F以及IL-22等细胞因子,在多种自身免疫性疾病和变态炎症反应中发挥作用,从而引起了Th1/Th2细胞的经典模式的调整[1]。目前,关于Th17细胞在变应性鼻炎(Allergic Rhinitis, AR)中的研究很少,其相关的变态反应机制尚不明确。本实验通过探讨AR小鼠与正常小鼠、IL-17抗体干预后的AR小鼠在行为学、组织病理学,Th1、Th2、Th17细胞相关免疫学细胞因子的数量以及Th17细胞特异性转录因子的表达水平,评价AR发病机制中Thl7细胞的可能作用及相关潜在的治疗方法。 研究方法选取BALB/c小鼠30只,雌雄各半,分别随机分为三组,对照组,模型组和干预组,每组10只。以卵清蛋白(Ovalbumin, OVA)经典致敏法制作模型组和干预组BALB/c小鼠AR模型,造模成功后干预组予IL-17抗体治疗。对照组以生理盐水替代同方法同剂量给药。采集外周血酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测并分析各组小鼠IL-17、IL-4和干扰素(Interferon-γ, IFN-γ)。并取鼻粘膜行反转录聚合酶链反应法(reverse transcriptase polymerase chain reaction, RT-PCR)测维甲酸相关孤儿核受体(Retinoic acid-related orphan receptorγt, RORγt)mRNA的表达水平及行苏木素-伊红(hematoxylin-eosin, HE)染色。实验结果以x-±s表示,采用SPSS13.0统计分析软件对三组数据符合正态性分布、方差齐的进行单因素方差分析及多组均数差别的多重比较(LSD法)。偏态或方差不齐的数据进行多组数据的Kruskal-Wallis检验,及Bonferroni法两两比较平均秩和。以P0.05为有统计学意义。 研究结果模型组和干预组小鼠均激发出典型的症状,按评分标准造模成功。干预组经过干预后,喷嚏明显减少,偶有流涕,挠鼻现象基本消失。三组小鼠症状学分析模型组评分高于对照组、干预组(q值分别为10.22、9.10,P值均0.05)。模型组小鼠血清中IL-17、IL-4及鼻粘膜RORγtmRNA的表达水平明显增高,与对照组相比差异有统计学意义(q/Z值分别为14.6、16.58、8.19,P值均0.05)；而IFN-γ水平明显降低(q=8.02,P0.05)。干预组IL-17、IL-4、RORγtmRNA的表达低于模型组(q/Z=11.03、13.90、6.95,P0.05)：而IFN-Y有所升高(q=6.94,P0.05),差异均具有统计学意义。造模后鼻黏膜组织病理学发生炎症性反应,纤毛中断、柱状细胞充盈、杯状细胞增多,血管扩张,腺体增生、扩张,粘液分泌增加,嗜酸性粒细胞浸润；干预组改善显著。 结论在AR超敏反应中,除了与大多数研究中一致的结果——关于AR中,Th1/Th2细胞因子平衡问的Th2细胞因子过度极化以外,Th17细胞的分化亦占优势,而Th1细胞受到抑制。在经过IL-17抗体干预后,Th2、Th17细胞免疫性细胞因子数量均明显减少,炎性反应减退。提示这种特异性抗体治疗有一定的有效性。这为变应性鼻炎的治疗学研究,提供了一个新的思路。说明抑制IL-17可以减轻变应性鼻炎的症状,而针对Th17细胞特异性转录因子RORγt的基因干预措施更可能成为有效阻止变应性鼻炎反应的重要治疗方法。
[Abstract]:The helper T helper (Helper T, Th) cell 17 is a new type of Th cell, and has been shown to be able to play a role in the reaction of various autoimmune diseases and perversion inflammation by producing cytokines such as interleukin (IL) 17A, IL-17F, and IL-22. So as to cause the adjustment of the classical mode of the Th1/ Th2 cells[1]. At present, the study of Th17 cells in allergic rhinitis (AR) is very low, and its associated allergic mechanism is not clear. In this experiment, the number of the related immunological cytokines and the expression level of Th17 cell-specific transcription factors in AR mice after the intervention of the IL-17 antibody in AR mice and normal mice and IL-17 antibody were discussed. To evaluate the possible effects of the Thl7 cells in the AR pathogenesis and the associated potential treatment methods. Thirty-one BALB/ c mice were randomly divided into three groups: control group, model group and intervention group. Methods: The AR model of BALB/ c mice in the model group and the intervention group were prepared by the classical sensitization method of Ovalbumin (Ovalbumin, OVA), and the model group and the intervention group were treated with IL-17 antibody treatment after the model was successfully established. In the control group, the same method and the same method were replaced with normal saline. Methods: IL-17, IL-4 and Interferon-1, IFN-1, IL-4 and Interferon-1, IFN-1 in each group were detected and analyzed by an enzyme-linked immunosorbent assay (ELISA). The expression levels of Retinoic acid-related receptor (t) mRNA and hematoxylin-eosin (HE) were measured by reverse transcription polymerase chain reaction (RT-PCR). The results of the experiment are as follows: The results of the experiment are as follows: The results of the experiment show that the data of the three groups accord with the positive distribution, the variance of the variance and the multiple comparisons (LSD) of the variance of the multiple groups of data in the three groups according to the statistical analysis software of SPSS13.0. ) the Kruskal-Wallis test of a plurality of sets of data is carried out on the data of the deviation state or the variance, and the average rank of the two comparison of the Bonferroni method And. The results of the study showed that the typical symptoms were stimulated in both the model group and the group of intervention group, and the typical symptoms were made according to the scoring criteria. The model is successful. After the intervention, the effect of the intervention group is obviously reduced, and the nasal discharge and the flexible nasal phenomenon are even. The group scores of the three groups were higher than that of the control group, and the value of the intervention group (q) was 10.22, 9.10 and P <0, respectively. In model group, the expression of IL-17, IL-4 and the expression of tmRNA in the nasal mucosa was significantly higher than that in the control group (the q/ Z value was 14.6, 16.58, 8.19, P <0.05), while the level of IFN-1 decreased significantly (q = 8.02, P0. The expression of IL-17, IL-4 and IL-4 in the intervention group was lower than that of the model group (q/ Z = 11.03, 13.90, 6.95, P0.05): while the IFN-Y increased (q = 6.94, P0.05). In order to study the significance of the study, the inflammatory reaction, the cilia interruption, the filling of the columnar cells, the increase of the goblet cells, the expansion of the vessels, the proliferation of the glands, the increase of the secretion of the mucus, the infiltration of the eosinophils, the change of the intervention group, Good results. Conclusion In AR hypersensitivity, the differentiation of Th17 cells is also dominant in addition to the excessive polarization of the Th2 cytokines in AR and Th1/ Th2 cytokine balance in AR hypersensitivity, while Th1 is thin. The number of Th2 and Th17 cellular immune cytokines was significantly reduced after the IL-17 antibody intervention. The response is reduced. It is suggested that this specific antibody will be treated with one. The efficacy of the invention. This provides a therapeutic study of allergic rhinitis. It is suggested that the suppression of IL-17 can alleviate the symptoms of allergic rhinitis, and the gene intervention measures for the specific transcription factor of Th17 cell are more likely to be more effective in the inhibition of allergic rhinitis.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R765.21
[Abstract]:The helper T helper (Helper T, Th) cell 17 is a new type of Th cell, and has been shown to be able to play a role in the reaction of various autoimmune diseases and perversion inflammation by producing cytokines such as interleukin (IL) 17A, IL-17F, and IL-22. So as to cause the adjustment of the classical mode of the Th1/ Th2 cells[1]. At present, the study of Th17 cells in allergic rhinitis (AR) is very low, and its associated allergic mechanism is not clear. In this experiment, the number of the related immunological cytokines and the expression level of Th17 cell-specific transcription factors in AR mice after the intervention of the IL-17 antibody in AR mice and normal mice and IL-17 antibody were discussed. To evaluate the possible effects of the Thl7 cells in the AR pathogenesis and the associated potential treatment methods. Thirty-one BALB/ c mice were randomly divided into three groups: control group, model group and intervention group. Methods: The AR model of BALB/ c mice in the model group and the intervention group were prepared by the classical sensitization method of Ovalbumin (Ovalbumin, OVA), and the model group and the intervention group were treated with IL-17 antibody treatment after the model was successfully established. In the control group, the same method and the same method were replaced with normal saline. Methods: IL-17, IL-4 and Interferon-1, IFN-1, IL-4 and Interferon-1, IFN-1 in each group were detected and analyzed by an enzyme-linked immunosorbent assay (ELISA). The expression levels of Retinoic acid-related receptor (t) mRNA and hematoxylin-eosin (HE) were measured by reverse transcription polymerase chain reaction (RT-PCR). The results of the experiment are as follows: The results of the experiment are as follows: The results of the experiment show that the data of the three groups accord with the positive distribution, the variance of the variance and the multiple comparisons (LSD) of the variance of the multiple groups of data in the three groups according to the statistical analysis software of SPSS13.0. ) the Kruskal-Wallis test of a plurality of sets of data is carried out on the data of the deviation state or the variance, and the average rank of the two comparison of the Bonferroni method And. The results of the study showed that the typical symptoms were stimulated in both the model group and the group of intervention group, and the typical symptoms were made according to the scoring criteria. The model is successful. After the intervention, the effect of the intervention group is obviously reduced, and the nasal discharge and the flexible nasal phenomenon are even. The group scores of the three groups were higher than that of the control group, and the value of the intervention group (q) was 10.22, 9.10 and P <0, respectively. In model group, the expression of IL-17, IL-4 and the expression of tmRNA in the nasal mucosa was significantly higher than that in the control group (the q/ Z value was 14.6, 16.58, 8.19, P <0.05), while the level of IFN-1 decreased significantly (q = 8.02, P0. The expression of IL-17, IL-4 and IL-4 in the intervention group was lower than that of the model group (q/ Z = 11.03, 13.90, 6.95, P0.05): while the IFN-Y increased (q = 6.94, P0.05). In order to study the significance of the study, the inflammatory reaction, the cilia interruption, the filling of the columnar cells, the increase of the goblet cells, the expansion of the vessels, the proliferation of the glands, the increase of the secretion of the mucus, the infiltration of the eosinophils, the change of the intervention group, Good results. Conclusion In AR hypersensitivity, the differentiation of Th17 cells is also dominant in addition to the excessive polarization of the Th2 cytokines in AR and Th1/ Th2 cytokine balance in AR hypersensitivity, while Th1 is thin. The number of Th2 and Th17 cellular immune cytokines was significantly reduced after the IL-17 antibody intervention. The response is reduced. It is suggested that this specific antibody will be treated with one. The efficacy of the invention. This provides a therapeutic study of allergic rhinitis. It is suggested that the suppression of IL-17 can alleviate the symptoms of allergic rhinitis, and the gene intervention measures for the specific transcription factor of Th17 cell are more likely to be more effective in the inhibition of allergic rhinitis.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R765.21
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相关期刊论文 前7条
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