低剂量茶碱对气道重塑的影响及其机制

Effect of Low Dose Theophylline on Airway Remoding

目的探讨低剂量茶碱对大鼠气道重塑的影响及其作用机制。方法 SD大鼠40只随机分为空白对照组,模型组,低剂量茶碱组,治疗剂量茶碱组,采集肺组织标本和血标本。ELASA法测定肺泡灌洗液中的EGF的活性、免疫组织化学染色法观察肺内气道TGF-β1的含量、肺组织内MMP2和肺内气道的NF-κB表达;采用高效液相色谱法检测大鼠血浆茶碱浓度。结果丙烯醛雾化可以增加大鼠肺泡灌洗液中的EGF的活性、肺内气道上皮细胞TGF-β1蛋白的含量及肺组织MMP2的含量,同时促进NF-κB入核。应用低剂量（5～10mg/L）和治疗剂量茶碱（10～20μg/mL）干预均可明显降低大鼠肺BLAF中EGF的活性、气道上皮细胞TGF-β1蛋白的含量、肺组织MMP2的含量和NF-κB的入核率,而低剂量和治疗剂量茶碱两组之间的干预作用无明显差异。结论低剂量与治疗剂量茶碱一样可抑制丙烯醛所致的气道重塑,其作用机制可能与抑制NF-κB的活化有关。

Objective To investigate the effect of low dose theophylline on airway remolding in rat model induced by inhaling acrolein and explore its mechanism.Methods The SD rats were randomly assigned into 4 groups（n = 10,respectively） ：control group,model group,low dose theophylline intervention group,therapy dose theophylline intervention group.Lung tissue were acquired after the rats were sacrificed on the 28st day.The epidermal growth factor（EGF） in lung lavage fluid was examined with ElASA.Transforming growth facter-β1（TGF-β1） contents were detected by immunohistochemisy.The expression of matrix metalloproteinase 2（MMP2） in lung tissue was observed with immunohistochemisy.Nuclear factor-κB（NF-κB） was assayed with immunohistochemisy.Concentration of theophylline in blood plasma was examined by high performance liquid chromatography.Results Acrolein inhalation could upregulate the liveness of EGF in lung lavage fluid of the rats,and it also increased TGF-β1contents of epithelial cell on airway and the contents of MMP2 in lung tissue.Meanwhile,it stimulated transfer of NF-κB.After intervened by low dose and therapy dose theophylline,all above-mentioned were obviously reduced.Conclusion The results suggested that low dose theophylline can suppress airway remolding caused by acrolein,which was likely related to the suppression of activation of NF-κB.