布地奈德对哮喘大鼠IKK/NF-κB信号通道影响的实验研究

Effects of budesonide on signal pathway of IKK/NF-κB in asthma rats

目的:观察布地奈德混悬液(Bud,商品名:普米克令舒)对哮喘大鼠肺组织IκB激酶(IKKβ)mRNA表达及核转录因子(NF-κB)活化的影响。方法:复制哮喘大鼠模型,分为正常组、哮喘组和布地奈德混悬液雾化组,用原位杂交法检测肺组织IKKβmRNA表达,免疫组化检测肺组织NF-κBp65蛋白活性,双抗体夹心酶联免疫法(ELISA)检测血清及支气管肺泡灌洗液(BALF)中IL5的浓度。结果:哮喘组肺组织IKKβmRNA(0.203±0.038)及NF-κBp65(0.256±0.063)表达量均显著高于正常组(分别为0.015±0.006,0.034±0.008,P<0.01)。布地奈德混悬液雾化组肺组织IKKβmRNA(0.101±0.010)和NFκBp65(0.062±0.014)表达均显著低于哮喘组(P均<0.01)。结论:哮喘组肺组织IKKβmRNA、NF-κBp65表达显著增强,Bud雾化吸入能有效抑制哮喘大鼠肺组织IKKβmRNA的表达及NF-κBp65的活性,证明Bud能有效抑制IKKNFκB信号通道的活性。

AIM: To study the role of budesonide in regulating asthma inflammation and the activity of IKKβmRNA and NF-κBp65 protein. METHODS: Thirty-six Sprague-Dawley (SD) rats were divided into three groups: normal group, asthmatic model group and budesonide (Bud) group (n=12 in each). The asthmatic model was established by ovalbumin (OVA) injection and inhalation. The rats in Bud group were administered budesonide atomized inhalation within 14 days. The mRNA expression of IKKβ and the protein NF-κBp65 in lung tissue were assessed by situ hybridization with oligonucleotide probe and immunohistochemisty, respectively. The concentration of interleukin 5 (IL-5) in serum and BALF were measured by sandwich ELISA. RESULTS: Twenty-four hours after the last antigen chenllenge, the mRNA expression of IKKβ( 0.203± 0.038)and the protein expression of NF-κBp65( 0.256± 0.063)in asthmatic group increased compared with control group ( 0.015± 0.006, 0.034± 0.008, P< 0.01, respectively). The mRNA expression of IKKβ ( 0.101± 0.010) and the protein expression of NF-κBp65( 0.062± 0.014)in Bud group decreased compared with asthmatic group (P< 0.01, respectively). CONCLUSION: In asthmatic rats, the expression of IKKβmRNA and the protein of NF-κBp65 were increased significantly, budesonide atomized inhalation can inhibit the expression of IKKβmRNA and the protein of NF-κBp65 and hold down the activity of the signal pathway IKK/NF-κB.