砷剂防治哮喘气道炎症的分子机制:砷剂对丝裂原活化蛋白激酶磷酸酶基因表达作用的研究

Molecular mechanism of arsenic trioxide in preventing and treating airway inflammation of asthma:effects of arsenic trioxide on the gene expression of mitogen activated protein kinase phosphatase

目的:研究三氧化二砷对T细胞丝裂原活化蛋白激酶磷酸酶(mitogen-activatedproteinkinasephosphatase,MKP-1)基因表达的影响,探讨砷剂治疗哮喘气道炎症的分子机制。方法:本研究采用定量PCR的技术研究Hut-78T细胞在不同浓度三氧化二砷(5μmol/L和1μmol/L)作用下,在不同时间段(3min,10min,20min,30min及1h),T细胞内MKP-1mRNA的表达水平。结果:Hut-78细胞在经过砷剂处理后,细胞内MKP-1mRNA水平在10min即呈现上升的趋势,5μmol/L砷剂20min组和1μmol/L砷剂20min组细胞内MKP-1mRNA水平均明显高于对照组(t=5.947,P=0.001;t=2.561,P=0.035),而在30min时,所诱导MKP-1mRNA水平均达到高峰,其后均呈下降的趋势。而在时间段20min和1h,5μmol/L砷剂组要高于1μmol/L组(t=3.056,P=0.0223;t=3.501,P=0.0128)。结论:三氧化二砷对MKP-1的基因表达具有上调作用;MKP-1为三氧化二砷作用的早期反应基因之一;砷剂对MKP-1的作用呈时间和剂量相关;小剂量的砷剂可能在哮喘的治疗和预防上具有重要的应用价值。

AIM:To study the effects of the arsenic trioxide(AT)on the gene expression of mitogen activated protein kinase phosphatase (MKP 1) in Hut 78 cells, and explore the molecular mechanism of AT in treating airway inflammation of asthma. METHODS: Hut 78 cells were stimulated with different concentrations of AT(5 μmol/L and 1 μmol/L) at 3, 10, 20, 30 minutes and 1 hour. Quantitative PCR was performed to investigate the gene expression of MKP 1 in the different time courses.RESULTS: The mRNA expression of MKP 1 began to increase in 10 minutes, the mRNA expression levels of MKP 1 in the 5 μmol/L and 1 μmol/L groups at 20 minutes were obviously higher than that in the control group(t=5.947,P=0.001;t=2.561,P =0.035), and then it reached the peak value at 30 minutes, then it showed a decreasing tendency, while the expression levels at 20 minutes and 1 hour were higher in the 5 μmol/L group than in the 1 μmol/L group(t=3.056,P=0.022 3;t=3.501,P=0.012 8).CONCLUSION: AT up regulates the gene expression of MKP 1. MKP 1 is one of the early response genes of AT;AT has the time and concentration dependant relation with MKP 1.AT of small dosage may be important in the treatment and prevention of asthma.