中文摘要：

目的研究铝致人神经母细胞瘤细胞（SH-SY5Y）死亡过程中MAPK信号通路的作用，探索铝致神经细胞死亡的机制。方法用4mmol／L的AlCl3·6H2O染毒SH-SY5Y细胞模拟铝致神经细胞死亡模型，用凋亡的特异性阻断剂zVAD-fmk（20μmol／L）抑制凋亡发生，用程序性坏死的特异性阻断剂necrostatin-1（Nec-1，60μmol／L）抑制程序性坏死发生，用CCK-8检测不同组间细胞活力的变化，用流式细胞术检测凋亡率及坏死率的差异，用蛋白印迹法检测MAPK信号通路蛋白磷酸化水平的改变。结果与空白对照组、溶剂对照组、zVAD—fmk对照组和Nec-1对照组相比，染铝组、凋亡抑制组和程序性坏死抑制组的细胞活力下降（P〈0．05）；与染铝组相比，程序性坏死抑制组和凋亡抑制组的细胞活力上升（P〈0．05）。与空白对照组、溶剂对照组、zVAD．fmk对照组和Nec-1对照组相比，染铝组、凋亡抑制组和程序性坏死抑制组的凋亡率和坏死率上升（P〈0．05）；与染铝组相比，凋亡抑制组和程序性坏死抑制组的凋亡率和坏死率下降（P〈0．05）。与空白对照组、溶剂对照组、zVAD—fmk对照组和Nec-1对照组相比，染铝组、凋亡抑制组和程序性坏死抑制组p38磷酸化水平升高，ERK磷酸化水平下降（P〈0．05）；与染铝组相比，程序性坏死抑制组的p38磷酸化水平下降，ERK磷酸化水平上升（P〈0．05）。结论MAPK信号通路中的p38和ERK信号通路参与了铝致SH—SY5Y细胞程序性坏死，ERK信号通路参与了铝致SH—SY5Y细胞凋亡。而JNK信号通路耒参与铝致SH—SYSY细胞死亡。

英文摘要：

Objective To explore the role of MAPK signaling pathway in apoptosis and necroptosis induced by aluminum in SH-SY5Y cells. Methods To imitate neural cell death induced by aluminium, AlCl3 ·6H2O （4 mmol/L） was used to treat SH-SYSY cells. Necrostatin-1 （Nec-1,60 μmol/L） ） , the specific inhibitor for necroptosis, and zVAD-fmk （20 μmol/L） , the specific inhibitor for apoptosis, were added into cultures for inhibiting the occurrence of necroptosis and apoptosis. CCK-8 was performed to measure cell viability, flow cytometry was used to test the difference of apoptosis rate and necrosis rate between groups,and western-blot was used to detect the change of MAPK protein. Results Compared with blank control group, solvent control group, Nec-1 control group and zVAD-fmk control group, cell viabiligy of Al^3＋ exposed group, Al^3＋ plus Nec-1 group and Al^3＋ plus zVAD-fmk group decreaced （ P 〈 0.05 ）. Compared with Al^3＋ exposed group, cell viability of Al^3＋ plus Nec-1 group and Al^3＋ plus zVAD-fmk group increased （P 〈 0.05 ）. Necrotic rate and apoptotic rate in Al^3＋ exposed group, Al^3＋ plus Nec-1 group and Al^3＋ plus zVAD-fmk group obviously increased compared with blank control group, solvent control group, Nec-1 control group and zVAD-fmk control group （ P 〈 0.05 ）. Compared with Al^3＋ exposed group, necrotic and apaptotic rate of Al^3＋ plus zVAD-fmk group and Al^3＋ plus Nec-1 group were statistically significant decreased （P 〈0.05）. Compared with blank control group, solvent control group, Nec-1 control group and zVAD-fmk control group, expression of p-p38 in Al^3＋ exposed group, Al^3＋ plus Nec-1 group and Al^3＋ plus zVAD-fmk group increased obviously（P 〈 0.05） , and expression of p-ERK decreased significantly （P 〈 0.05 ）. Compared with Al^3＋ exposed group, expression of p-p38 decreased（P 〈 0.05 ） , but p-ERK increased in Al^3＋ plus Nec-1 group （P 〈0.05）. Conclusion The ERK and p38 MAPK signaling pathways are involved i