GATA-3在大鼠哮喘模型气道炎症中作用的实验研究

目的：探讨GATA-3在Wistar大鼠哮喘模型气道炎症中的作用。 方法： 按常用方法复制大鼠哮喘模型并分为哮喘组(A组)，地塞米松治疗组（D组），反义寡核苷酸治疗组（AS组），无意义寡核苷酸治疗组（NS组）和正常对照组（N组）5组，每组10只。反义寡核苷酸和无意义寡核苷酸经鼻气管内给药，地塞米松腹腔注射给药。HE染色方法观察气道炎症变化。免疫组化方法观察GATA-3阳性细胞数。用RT-PCR方法观察大鼠肺组织GATA-3 mRNA表达。用Western 蛋白印迹法检测肺组织中GATA-3蛋白质表达。 结果： A组GATA-3 mRNA和蛋白质的表达量及气道嗜酸性粒细胞浸润数量明显大于N组（P<0.01）。AS组和D组GATA-3 mRNA和蛋白质表达量及气道嗜酸性粒细胞浸润数量均明显低于A组（P<0.01）。NS组GATA-3 mRNA和蛋白质表达量和嗜酸性粒细胞浸润数量与A组相比差异无显著（P>0.05）。GATA-3的表达与大鼠支气管肺组织中嗜酸性粒细胞浸润数量呈正相关，r=0.995(P<0.01)。 结论： GATA-3反义寡核苷酸能特异性地抑制GATA-3基因的表达，减轻气道炎症反应。GATA-3 在Wistar大鼠哮喘模型效应阶段气道炎症中具有重要作用。

Role of GATA-3 in the pathogenesis of airway inflammation in a rat asthma model

AIM: To investigate the role of GATA-3 in the pathogenesis of airway inflammation in a Wistar rat asthma model.METHODS: The Wistar rat asthma model was made with conventional method and animals were divided into five groups(10 rats in each group): asthma group(A group),dexamethasone group(D group),antisense oligonucleotide group(AS group),nonsense oligonucleotide group(NS group) and normal control group(N group).Antisense,nonsense oligonucleotide were administered intranasally,and the dexamethasone was injected intraperitoneally.The airway inflammation was observed with HE staining method.The GATA-3 positive cells were stained immunohistochemically.The GATA-3 mRNA expression in pulmonary tissue was investigated with RT-PCR.The GATA-3 protein in pulmonary tissue was detected by Western blotting.RESULTS: In contrast to N group,the expression of GATA-3 mRNA, protein and the amount of inflammatory cells in pulmonary tissue in group A were increased significantly(P<0.01) and were decreased evidently in group AS and D(P<0.01).The expression of GATA-3 mRNA,protein and the amount of inflammatory cells in NS group were obviously increased compared with those in gropu AS and D(P<0.01).The expression of GATA-3 was related to the amount of eosinophils(r=0.995).CONCLUSION: GATA-3 antisense oligonucleotide blocks the expression of GATA-3 gene and the infiltration of eosinophils.GATA-3 plays an important role in the effector phase of allergic airway inflammation in a Wistar rat asthma model.