支气管哮喘豚鼠肺组织中KLF2的表达及意义

Expression of KLF2 in Lung Tissue of Guinea Pigs with Bronchial Asthma and Its Significance

目的:探讨锌指Krüppel样转录因2(KLF2)在豚鼠支气管哮喘肺组织中的表达及意义。方法:30只健康雄性豚鼠,按随机数字表法分为对照组(A组)、哮喘组(B组)及地塞米松治疗组(C组),每组10只。卵清蛋白致敏法复制哮喘模型。观察豚鼠肺组织病理学改变,BALF细胞总数及分类计数;采用原位杂交和RT-PCR检测肺组织中KLF2的mRNA表达情况,免疫组化和Westernblot检测肺组织中KLF2的蛋白表达水平。结果:(1)哮喘组豚鼠BALF中细胞总数、嗜酸性粒细胞百分比(EOS%)、中性粒细胞百分比(NEU%)显著高于对照组(P<0.01),哮喘组肺组织可见大量炎症细胞浸润,及明显气道重塑改变,而地塞米松治疗组BALF炎细胞浸润及肺组织病理改变较哮喘组明显减轻;(2)KLF2mRNA和蛋白在哮喘组表达显著低于对照组,在地塞米松治疗组中的表达明显高于哮喘组,3组差异均有统计学意义(P均<0.01);(3)KLF2蛋白以及mRNA与肺泡灌洗液炎细胞总数及EOS%,NEU%呈负相关。结论:KLF2在支气管哮喘急性发作期模型中表达明显下降,而地塞米松治疗后KLF2的表达上调,提示KLF2可能在支气管哮喘的发病机制与防治中起重要作用。

Objective：To investigate the expression and significance of KLF2 in lung tissue of guinea pigs with Bronchial Asthma.Methods：Thirty healthy male guinea pigs were randomly divided into 4 groups：the control group（group A）,asthmatic group（group B）,Dexamethasone group（group C）,10 guinea pigs in each group.The asthmatic model was established by the ovalbumin challenge method.Before determining the total number of BALF cells and cells classification,the changes in lung histopathology were observed.Expressions of KLF2 mRNA in lung tissue were assayed by in situ hybridization and by RT-PCR;Expressions of KLF2 protein were detected by immunohischemistry and by Western blot.Results：（1）The total number of inflammatory cells and EOS%,NEU% in BALF of asthma group were significantly higher than those of control group（P0.01）,and large numbers of inflammatory cell infiltration and obviously bronchiole remodeling response could be seen in this group.However,all these changes were obvious decreased after Dexam-ethasone treatment.（2） Protein and mRNA expressions of KLF2 in asthma group significantly higher than those in control group（P0.01）,and those in Dexamethasone group was markedly increased compared to asthma group（all P 0.01）.（3） Linear correlation analysis showed that KLF2mRNA and protein was negatively correlated with EOS%,NEU% and the total number of inflammatory cells in BALF（r=0.524,P 0.01）.Conclusions：In acute exacerbation of Bronchial Asthma model induced by ovalbumin,the study showed that asth-matic guinea pigs have significantly decreased expressions of KLF2,which up-regulated by Dexamethasone treatment group,suggesting that KLF2 may play an important role in the pathogenesis and prevention of Bronchial Asthma.