二烯丙基三硫通过NF-κB抑制脂多糖诱导小鼠肺组织IL-1β表达

Diallyl trisulfide inhibites interleukin-1β expression induced by lipopolysaccharide through inhibiting NF-κB activation in murine lung

目的探讨核因子-κB(NF-κB)在二烯丙基三硫(DATS)抑制脂多糖(LPS)致急性肺损伤(ALI)小鼠IL-1β表达中的作用。方法小鼠随机分为对照组、ALI组、DATS组、DATS预防组和DATS治疗组。RT-PCR检测肺组织中IL-1βmRNA表达。电泳迁移率改变(EMSA)检测肺组织NF-κB活性,Western blot检测肺组织中磷酸化及非磷酸化IκB的表达。结果ALI组小鼠肺组织中IL-1βmRNA表达明显升高(P<0.01),NF-κB活性及磷酸化IκB表达也明显高于对照组(P<0.05)。DATS预防组可显著抑制肺组织中IL-1βmRNA表达(P<0.05)、NF-κB活性及磷酸化IκB表达(P<0.05),但DATS治疗组的抑制效果不明显。结论DATS可通过抑制LPS诱导的IκB磷酸化及随后的NF-κB活化,进而抑制ALI小鼠肺组织IL-1βmRNA表达,这是DATS发挥抗ALI作用的信号传导机制之一。

Objective To investigate the role of nuclear factor-kappa B （NF-KB） in the modulation of diallyl trisul- fide （DATS） on interleukin-1β （IL-1β） expression induced by lipopolysaccharide （LPS） in mice with acute lung injury （ALI）. Methods Mice were randomly divided into Control group, ALI group, DATS group, DATS prevention group and DATS treatment group. The expression of IL-1β mRNA in the lung tissue was detected by reverse transcription PCR （RT-PCR）. NF-KB activity in the lung tissue was detected by electrophoresis mobility shift assay （EMSA）. The expression of phospho-IKB and IKB were assayed by Western blot. Results The expression of IL-1β mRNA, NF-KB activity and the phospho-IKB expression in lung tissues increased significantly at ALI group （P 〈 0. 01, P 〈 0. 05 ）, which were significantly inhibited by pretreatment of DATS with ALI mice （P 〈 0. 05 ）. However, no significant change was found in DATS treatment group. Conclusion Pretreatment of DATS with ALI mice downregulates IL-1β mRNA expression by inhibiting phospohrylation of IKB and the subsequent NF-KB activation in lung tissues of ALI mice induced by lipopolysaccharide, which is one of the signal transduction mechanisms of DATS to prevent the occurrence of ALI.