甲基化酶抑制剂对变应性鼻炎大鼠Th1/Th2细胞及相关因子的影响  

Effects of methylase inhibitors on Th1/Th2 cells and related factors in allergic rhinitis rats

作　　者：梁晓鹰 姜孝芳[1] 单彩霞 高丽[1] Liang Xiaoying;Jiang Xiaofang;Shan Caixia;Gao Li(College of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi 83000,China)

机构地区：[1]新疆医科大学中医学院,乌鲁木齐83000

出　　处：《国际免疫学杂志》2021年第1期35-40,共6页International Journal of Immunology

基　　金：国家自然科学基金(81260006);新疆医科大学研究生创新创业项目(CXCY2017041)。

摘　　要：目的探讨甲基化酶抑制剂5-杂氮-2-脱氧胞苷(5-aza-2-deoxycytidine,5-aza)对变异性鼻炎大鼠辅助性T细胞(helper T cell,Th)亚群Th1和Th2细胞的分化及白细胞介素(interleukin,IL)-4、干扰素(interferon,IFN)-γ水平表达的影响。方法将30只SD雄性大鼠随机分为3组:正常组、模型组、5-aza组,每组10只。予以卵清蛋白致敏的方法建立变应性鼻炎模型,分别干预后采血行流式细胞术检测Th1、Th2细胞比率,酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测Th1细胞分泌的细胞因子IFN-γ和Th2细胞分泌的细胞因子IL-4的表达,并留取鼻粘膜行苏木精-伊红染色法(hematoxylin-eosin staining ,HE)染色。结果流式细胞术检测结果显示,模型组中Th2细胞的比率均较5-aza组和正常组明显升高[(7.28±1.37)%比(6.17±1.06)%,(6.05±0.95)%,F=2.920,P<0.05],差异具有统计学意义;5-aza组Th2细胞的比率明显低于模型组,差异具有统计学意义(P=0.039);模型组、5-aza组和正常组的Th1细胞比率差异无统计学意义(P>0.05)。ELISA法检测结果显示,模型组大鼠IL-4的表达水平明显高于正常组和5-aza组,差异具有统计学意义[(175.19±10.14) pg/mL比(160.14±16.86) pg/mL,(160.75±17.45)pg/mL,F=2.743,P<0.05)]。5-aza组IL-4的表达水平较模型组明显降低(P=0.047),但三组间IFN-γ的表达表达水平差异无统计学意义(P>0.05)。HE染色光镜下可见,正常组大鼠鼻粘膜组织结构完整、清晰,鼻粘膜无水肿,充血;模型组鼻粘膜固有层充血、水肿,粘膜下层腺体增生,血管增生,并有大量炎性细胞及嗜酸性粒细胞浸润,鼻粘膜纤毛破坏;5-aza组鼻粘膜组织结构大致完整,可见少量嗜酸性粒细胞浸润。结论甲基化酶抑制剂能有效缓解大鼠过敏性鼻炎症状,减轻过敏大鼠的鼻粘膜组织损伤。提示甲基化酶抑制剂可能使得Th2表达下调抑制炎性反应。Objective To investigate the effects of 5-aza-2-deoxycytidine(5-aza)on the differentiation of helper T cell(Th1)and Th2 cells and the expression of interleukin(IL)-4 and interferon(IFN)-γin rats with variant rhinitis.Methods Thirty SD male rats were randomly divided into 3 groups:normal group,model group and 5-aza group with 10 rats in each group.Allergic rhinitis model was established by ovalbumin sensitization.After intervention,blood samples were collected for flow cytometry to detect the ratio of Th1 and Th2 cells,and enzyme linked immunosorbent assay(ELISA)was used to detect the expression of cytokine IFN-γsecreted by Th1 cells and IL-4 secreted by Th2 cells.The nasal mucosa was stained with hematoxylin eosin staining(HE).Results The results of flow cytometry showed that the ratio of Th2 cells in model group was significantly higher than that in 5-aza group and normal group[(7.28±1.37)%vs(6.17±1.06)%vs(6.05±0.95)%,F=2.920,P<0.05].The ratio of Th2 in the 5-aza group was significantly lower than that in the model group(P=0.039).There was no significant difference in the Th1 ratio among the three groups(P>0.05).The results of ELISA showed that the expression level of IL-4 in the model group was significantly higher than that in the normal group and 5-aza group[(175.19±10.14)pg/mL vs(160.14±16.86)pg/mL,(160.75±17.45)pg/mL,F=2.743,P<0.05].The expression level of IL-4 in 5-aza group was significantly lower than that in model group(P=0.047).There was no significant difference in IFN-γexpression among the three groups(P>0.05).The light microscope of HE staining showed that the structure of nasal mucosa was complete and clear,without edema and hyperemia in the normal group.In the model group,hyperemia and edema of lamina propria,hyperplasia of glands and blood vessels in submucosa,infiltration of inflammatory cells and eosinophils,and destruction of nasal mucosa cilia were observed.In the 5-aza group,the nasal mucosa was almost intact with a small amount of eosinophils.Conclusion Methylase inhibitors can eff

关 键 词：变应性鼻炎 甲基化酶抑制剂 表观遗传 白细胞介素-4 干扰素-Γ 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]