Toll样受体4/核因子-κB对哮喘大鼠气道炎症和重构的影响

Effect of TLR4/NF-κB on airway inflammation and airway remodeling in rat model of asthma

目的:探讨TLR4/NF-κB对哮喘大鼠气道炎症和气道重构的影响。方法:将18只SD大鼠随机分成3组:对照组、哮喘4周组和哮喘8周组,每组6只。造模成功后,利用HE染色、免疫组织化学方法及病理图像分析系统分析大鼠气道平滑肌的嗜酸性粒细胞(EOS)浸润情况、气道壁厚度以及增殖细胞核抗原(PCNA)和Bcl-2的蛋白表达量。利用RT-PCR和Western blotting检测ASM中TLR4和NF-κB的mRNA及蛋白表达。结果:哮喘4周组和哮喘8周组的气道壁EOS计数、气道壁厚度、气道反应性均较正常对照组显著增加(P<0.01);哮喘4周组和哮喘8周组的TLR4及NF-κB的mRNA水平和蛋白表达与对照组比较均显著增加(P<0.01);TLR4及NF-κB的mRNA水平随哮喘天数的增加而显著增加(P<0.01);哮喘4周组、哮喘8周组PCNA和Bcl-2的蛋白表达量均显著高于正常对照组(P<0.01);哮喘两组间上述指标差异显著(P<0.05或P<0.01)。结论:TLR4/NF-κB可能参与哮喘大鼠气道炎症和气道重构的调控。

AIM： To explore the effect of TLR4/NF-κB on airway inflammation and airway remodeling in a rat asthma model.METHODS： Eighteen SD rats were divided into 3 groups（n=6）： control group,asthmatic 4 weeks group and asthmatic 8 weeks group.The methods of HE staining,immunohistochemistry and pathology image analysis were used to detect the changes of eosinophile granulocytes（EOS）,the thickness of airway wall and the expression of proliferating cell nuclear antigen（PCNA） and Bcl-2 in the airway smooth muscle in asthmatic rats.The expression of TLR4 and NF-κB at mRNA and protein levels in the airway smooth muscle was determined by RT-PCR and Western blotting.RESULTS： The EOS,the thickness of airway wall and airway reactivity in asthmatic group were significantly higher than those in control group.The expression of TLR4 and NF-κB at mRNA and protein levels in asthmatic group was significantly higher than those in control group.The protein levels of PCNA and Bcl-2 were significantly higher than those in control group.Significant difference between two asthmatic groups was observed in the above indexes.CONCLUSION： TLR4 /NF-κB may regulate the airway inflammation and airway remodeling in asthmatic rats.