咪喹莫特抑制哮喘大鼠气道炎症转录水平的研究

A study of mRNA expression on imiquimod in the inhibition of asthmatic airway inflammation in rat

目的 探讨咪喹莫特拮抗支气管哮喘气道炎症的分子机制。方法 卵清蛋白腹腔注射与雾化吸入建立大鼠哮喘模型,采用逆转录-聚合酶链反应(RT-PCR)测定了不同剂量咪喹莫特对哮喘大鼠肺组织白介素(IL)-4mRNA、IL-5mRNA、IL-12mRNA和干扰素(IFN)-γmRNA表达的影响。结果 咪喹莫特各治疗组及地塞米松组能显著抑制哮喘大鼠肺组织中IL-4、IL-5mRNA的表达(与哮喘组比,均为P<0.001;与空白对照组比,均为P>0.05),各咪喹莫特组同时能显著增加IL-12、IFN-γmRNA表达(与哮喘组比,均为P<0.001;与空白对照组比,均为P>0.05),而地塞米松组不能增加IL-12、IFN-γ mRNA的表达(与哮喘组比,均为P>0.05;与空白对照组比,均为P<0.001)。咪喹莫特各治疗组间无显著性差异。结论 咪喹莫特能降低哮喘大鼠肺组织中IL-4和IL-5基因转录,增加IL-12和IFN-γ基因转录,进而抑制嗜酸性粒细胞的聚集、活化,发挥其抗气道炎症的作用。

Objective To investigate the molecular mechanism of effect of inhaled imiquimod on ovalbumin(OVA)-induced allergic airway inflammation in rat model. Methods An animal model of asthma was established by OVA sensitizing-challenging SD rat. The expression levels of IL- 4,5, 12mRNA and IFN-γ mRNA in lung tissues in asthmatic rats treated with different dosages of imiquimod were examined semi-quantitatively by reverse transcription-polymerase chain reaction (RT-PCR). Results The levels of the expression of IL- 4,5mRNA in lung tissues were significantly decreased in each dose of imiquimod-treated group and dexamethasone-treated group( compared with the asthma group,all P<0. 001 ; compared with the normal group,all P>0. 05). Compared with the asthma group,the levels of the expression of IL-12,IFN-γ mRNA in lung tissues in the imiquimod-treated groups were highertall P<0. 001) ,but were lower in the dexamethasone-treated group(P>0. 05). No significant differences were seen among the three different dosages of imiquimod-treated groups. Conclusion Imiquimod shows its effect on anti-airway inflammation by marked inhibition of the expression levels for IL- 4,5mRNA and significantly increasing the expression levels for IL-12. IFN-γ mRNA, inhibition of eosinophilic aggregation and activation in the airway.