甲醛诱导哮喘的一种分子机理:对GSNO还原酶的上调作用

A Molecular Mechanism of Formaldehyde-Induced Asthma: Up-regulation of GSNO Reductase

为了研究气态甲醛对GSNO还原酶(GSNOR)的上调作用是否通过GSH途径,以昆明雄性小鼠为实验材料,采用动态吸入染毒方式,检测了0、3.0mg·m-3甲醛暴露小鼠以及3.0mg·m-3甲醛暴露同时腹腔注射α-硫辛酸小鼠的肺泡灌洗液中GSH浓度和GSNOR活力.结果表明,3.0mg·m-3甲醛暴露小鼠与对照组小鼠相比,其肺泡灌洗液中GSNOR活力极显著上升(p<0.01),同时GSH浓度极显著下降(p<0.01);α-硫辛酸注射组小鼠肺泡灌洗液中GSNOR活力较3.0mg·m-3甲醛暴露小鼠有极显著下降(p<0.01),同时GSH浓度极显著上升(p<0.01).甲醛暴露下,GSNOR与GSH呈相反的变化趋势.以上结果表明,气态甲醛可以通过GSH途径调节GSNOR表达.甲醛对GSNOR的上调作用可能是通过诱导氧化胁迫进行的,这可能是理解GSNOR在气道中调控的基础.

In order to investigate whether the up-regulation of GSNO reductase （GSNOR） by gaseous formaldehyde is associated with the changes of GSH levels, the Kunming male mice were used as experimental materials in present study. GSNOR activity and GSH levels were measured in bronchoalveolar lavage of mice after the exposure to 0, 3.0mg ·m^-3 formaldehyde and mice that were intraperitoneally injected with α-lipoic acid. The results showed that GSNOR activity was significantly increased in 3.0mg ·m^-3 formaldehyde inhaled mice, accompanied with the significant decrease of GSH levels （compared with 0mg ·m^-3 formaldehyde inhaled mice p〈0.01） ; while α-lipoic acid injection resulted in a significant decrease of GSNOR activity and increase of GSH levels in formaldehyde inhaled mice. After the exposure of formaldehyde, GSNOR and GSH showed an opposite tendencyl The results suggested that gaseous formaldehyde regulated GSNOR via GSH pathway. Formaldehyde might up-regulate GSNOR by inducing oxidative stress, which might provide a basis for the understanding of the regulation of GSNOR in the airways.