JNK信号通路在二甲基肿酸所致人胚肺成纤维细胞DNA损伤与凋亡中的作用

[目的]探讨c-Jun氨基末端激酶（JNK）信号通路在二甲基胂酸（DMA）所致人胚肺成纤维（HELF）细胞DNA损伤与凋亡中的作用。[方法]以0、2．5、5、10和20μmol／LDMA处理HELF细胞48h后，检测HELF细胞生长、DNA损伤、细胞凋亡、JNK磷酸化水平；并用20μmol／LJNK抑制剂SP600125预处理30min后，再用DMA处理HELF细胞48h，观察上述指标变化情况。[结果]10和20μmol／LDMA对HELF细胞生长产生明显抑制作用（P〈0．05）；2．5、5、10和20μmol／LDMA引起HELF细胞γ-H2AX表达水平明显增强（P〈0．05），并具有一定剂量-效应关系（经直线相关分析，r=-0．982，P〈0．05）；5、10和20μmol／LDMA引起HELF细胞断裂，caspase3表达水平明显增强（P〈0．05），呈一定剂量-效应关系（经直线相关分析，r=0．945，P〈0．05）；5、10和20μmol／LDMA处理HELF细胞48h后，JNK磷酸化的表达水平明显增加（P〈0．05），呈现一定剂量-效应关系（经直线相关分析，r=0．988，P〈0．05）；JNK抑制剂SP600125能明显降低10、20μmol／LDMA的生长抑制作用（P〈0．05）；JNK抑制剂SP600125可明显阻滞DMA所致HELF细胞对DNA损伤和诱导的凋亡作用（P〈0．05）。[结论]DMA可引起HELF细胞DNA损伤和凋亡；在此过程中JNK信号通路激活起到正调控作用。

Effects of JNK Signaling Pathway on Dimethylarsinic Acid-induced DNA Damage and Apoptosis of Lung Fibroblast Cells in Human Embryo

[ Objective ] To investigate the effects of c-Jun NH2-terminal kinase （JNK） signaling pathway on dimethylarsinic acid （ DMA ）-induced DNA damage and apoptosis in human embryo lung fibroblast（ HELF ）cells. [ Methods ] After HELF cells were treated with control, 2,5, 5, 10 and 20 μmol/L DMA for 48 h, the indices of cellular proliferation, DNA damage, apoptosis and the levels of JNK phosphorylation were detected. The indices were examined in HELF cells treated with DMA after HLEF cells were previously treated with 20μmol/L JNK inhibitor, SP600125, for 30min. [ Results ] After exposure to DMA for 48 h, DMA markedly attenuated the proliferation at the concentration of 10, 20 μmol/L （P 〈 0.05 ）. The levels of phosphor-H2AX were significantly increased with 2.5, 5, 10 and 20μmol/L DMA in a concentration-dependent manner（ r=-0.982, P 〈 0.05 ）. The cleaved caspase3 levels were elevated at concentrations of 5, 10 and 20 μmol/L in a concentration-dependent manner（ r=-0.945, P 〈 0.01 ）. Phospho-JNK levels were significantly elevated with 5, 10, and 20μmol/L DMA in a concentration- dependent manner（ r=-0.988, P 〈 0.05 ）, Blocking of JNK pathway with SP600125 attenuated DMA-induced cell growth inhibition and significantly degraded DMA-induced DNA damage and cell apoptosis （P 〈 0.05 ）. [ Conclusion ] DMA induces DNA damage and cell apoptosis in HELF cells and JNK pathway up-regulates DNA damage and cell apoptosis.