过氧化氢刺激视网膜神经细胞凋亡的MAPK/AP1信号通路参与机制

MAPK/AP1 Signaling Pathway Involved in Hydrogen Peroxide Stimulated Retinal Nerve Cell Apoptosis

目的本文对过氧化氢刺激视网膜神经细胞凋亡的MAPK/AP1信号通路参与机制进行研究,为相关治疗提供参考。方法分离培养大鼠视网膜神经细胞至生长状态良好:细胞随机分为3组:对照组(control,n=9)、过氧化氢处理组(Hyd Per,n=9)、MAPK信号通路抑制剂PD98059组(PD98059,n=9)。各组细胞给予相应处理后分析各组视网膜神经细胞中细胞凋亡蛋白及MAPK/AP1信号通路蛋白的表达。结果与对照组相比,过氧化氢刺激后视网膜神经细胞Bcl2的表达明显降低(P<0.01),而Bax、Caspase6、Ras、Raf、MEK、ERK1/2及c-fos及c-jun的表达明显增强(P<0.01),DHE染色后细胞的荧光强度明显增强,且PD98059处理后上述异常明显恢复(P<0.01)。结论过氧化氢刺激视网膜神经细胞发生明显的细胞凋亡,且此过程与MAPK/AP1信号通路的过度活化有关。

Objective To study the mechanism by which MAPK/AP1 signaling pathway is involved in hydrogen peroxide stimulated retinal nerve cell apoptosis.Methods Rat retinal neurons were isolated and cultured to grow well. The cells were randomly divided into three groups： the control group（ control,n = 9）,the hydrogen peroxide treatment group（ Hyd Per,n = 9）,and the MAPK signaling pathway inhibitor PD98059 group（ PD98059,n = 9）. The cells in each group were given corresponding treatment to determine the expression of apoptotic protein and MAPK/AP1 signaling pathway protein in retinal neurons. Results Compared with the control group,the expression of Bcl2 in the retinal nerve cells decreased significantly（ P 0.01）,while the expressions of Bax,Caspase6,Ras,Raf,MEK,ERK1/2,c-fos and c-jun increased significantly（ P〈0.01）. The fluorescence intensity of the cells after DHE staining was obviously enhanced,and the above abnormality was obviously restored after treatment. Conclusion Hydrogen peroxide stimulates retinal neuron apoptosis, which is related to the excessive activation of MAPK/AP1 signaling pathway.