铝致大鼠皮层神经元凋亡及应激活化蛋白激酶活性的变化

目的：探讨氯化铝（AlCl3）对大鼠皮层神经元凋亡的诱导作用及其与应激活化蛋白激酶，又称c-jun氨基末端激酶（SAPK／JNK）信号转导通路的关系。方法：原代无血清培养至第7天，用不同剂量AlCl3(0、10、100、1000μmol/L）处理大鼠皮层神经元48h，然后用琼脂糖凝胶电泳及AnnexinⅤ联合PI染色法检测细胞凋亡；用免疫印迹法(Western blot)检测SAPK／JNK磷酸化水平的时间变化规律。结果：各染铝组均出现DNA ladder这一典型的凋亡特征，且随剂量增加渐趋明显，各剂量组细胞凋亡率明显升高，与对照组相比差异有显著性（P＜0．05），呈明显的剂量－效应关系。6h时SAPK／JNK磷酸化程度达到最高，以后逐渐降低，呈时间－效应关系（P＜0．05）。结论：铝诱导大鼠皮层神经元凋亡可能与SAPK／JNK信号转导通路有关。

Induction of apoptosis and change of the activity of SAPK/JNK in rat cortical neurons treated by aluminum chloride

Objective To explore the effect of aluminum chloride (Aids) on the apoptosis induction in rat cortical neurons, namely its relationship with the SAPK/JNK signaling pathway. Methods On the 7th day, A1C13 was incubated with cultured neurons at the dosage of 0,10,100, 1 000mol/L for 48 hours, then agarose gel electrophoresis of soluble DNA and the method of annexin V and PI combination labeling were used to measure the apoptosis. The time changes of phosphorylation of SAPK/JNK were examined by Western blot analysis. Results DNA ladder occurred in every treatment group. As the dosage of AlCl3 increased, DNA ladder appeared to be more and more obvious. The rates of apoptosis in cortical neurons in every treatment group were higher than those of control(P < 0.05) , having a significant dose-response relationship( P < 0.01) . The phosphorylation of SAPK/JNK reached its climax when cortical neurons had incubated with 1 mmol/L AlCl3 for 6 hours, and then it dropped gradually. The phosphorylation of SAPK/JNK appeared to have time-effect relationship( P < 0.05). Conclusion It suggested that apoptosis induced by aluminum in rat cortical neurons might be associated with the signal transduction pathway of SAPK/JNK.