N-乙酰半胱氨酸对哮喘小鼠肺组织HMGB1、RAGE表达的影响

Effect of N-acetylcysteine on HMGB1 and RAGE expression in the lungs of asthmatic mice

目的检测高迁移率族蛋白B1(HMGB1)及晚期糖基化终产物受体在小鼠哮喘模型肺组织表达及分布,以及N-乙酰半胱氨酸(NAC)对其影响。方法SPF级雌性BALB/c小鼠随机分为对照组、哮喘组及哮喘+NAC处理组,每组7只。建立哮喘模型,用RT-PCR法检测肺组织HMGB1及晚期糖基化终产物mRNA表达水平,免疫组化法检测两者在肺组织的分布。结果HMGB1mRNA表达在3组中分别为0.88±0.02,0.86±0.05,0.98±0.05;晚期糖基化终产物mRNA表达在3组中分别为1.20±0.20,1.21±0.08,1.58±0.21。相对于对照组,哮喘组的HMGB1和晚期糖基化终产物表达未发生显著性改变(P>0.05);相对于对照组和哮喘组,两者在NAC组表达均显著增加,具有统计学意义(P<0.05)。免疫组化染色可见HMGB1主要分布于支气管及肺泡上皮细胞,在细胞核、胞浆及胞膜均可见。晚期糖基化终产物主要分布于肺泡上皮,表达于胞膜上。结论HMGB1及其受体晚期糖基化终产物介导的信号转导通路可能参与哮喘气道氧化应激,但其确切的调控机制及在哮喘中的作用尚待深入研究。

Objective To investigate the expression of HMGB1 and RAGE mRNA in the lungs of asthmatic mice and the effect ofN-acetylcysteine （NAC） on their expression. Methods Twenty-one female BALB/c mice were randomly divided into control group, asthma group and NAC group （n=7）. The expressions of HMGB1 and RAGE mRNA and their distributions in the lungs were detected by RT-PCR and immunohistochemical method. Results The expression levels of HMGB1 and RAGE mRNA were not significantly different between the control group （0.88±0.02 and 1.20±0.20, respectively） and the asthma model group （0.86±0.05 and 1.21±0.08, P〉0.05）. After NAC treatment, both of HMGB1 and RAGE mRNA levels （0.98±0.05 and 1.58±0.21） were significantly higher than those in the other two groups （P〈0.05）. HMGB1 was found in the nuclei and membrane of the bronchial and alveolar epithelial cells, and RAGE was located on the membrane of the alveolar epithelial cells. Conclusion HMGB 1 and RAGE may play a role in the oxidative stress during asthma, but the exact mechanism needs further investigation.