【摘要】 目的探究铜、铁、锌、铝对人神经母细胞瘤细胞（SH-SY5Y）的神经毒性作用和机制。方法采用50、200、400μmol/L CuSO₄,1、2、4 mmol/L FeSO₄和Al Cl₃,50、100、200μmol/L ZnSO₄分别作用于SH-SY5Y细胞,通过噻唑蓝（MTT）法检测细胞生长活性。采用ELISA法检测细胞内Akt、磷酸化Akt（Ser473）、GSK-3β及磷酸化GSK-3β（Ser9）蛋白的表达。采用Annexin-V/PI双染法检测细胞凋亡率。结果铜、铁、锌、铝能明显抑制细胞活性,并呈剂量依赖性,与对照组比较差异有统计学意义（P<0.05）。铁和铝各剂量组Akt表达较对照组降低（P<0.05）;各剂量组GSK-3β表达无明显差异（P>0.05）;各剂量组Akt及GSK-3β的磷酸化水平低于对照组（P<0.05）。细胞凋亡率随染铜、铁、锌、铝剂量的加大而升高（P<0.05）。结论铜、铁、锌、铝可引起神经细胞毒性,抑制Akt活性,激活蛋白激酶GSK-3β,导致细胞凋亡。更多还原

【Abstract】 Objective To explore the effects of copper,iron,zinc and aluminum on the neurotoxi-city and mechanism in SH-SY5 Y cells. Methods SH-SY5 Y cells were treated with different concentrations of copper sulfate( 50,200,400μmol/L),iron sulfate and aluminum chloride( 1,2,4mmol/L),and zinc sulfate( 50,100,200 μmol/L) respectively. Cell viabilities were measured by MTT assay. ELISA kit method were performed to evaluate the deliverances of glycogen synthase kinase-3β( GSK-3β),phosphorylation of the sites in GSK-3β-Ser9,Akt and phosphorylated Akt( Ser473). The apoptosis rate of detected cells was by double-staining with Annexin-V and PI. Results With the increase of the concentration of copper,iron,zinc and aluminum increased,the viability of SH-SY5 Y cell decreased gradually. The cell viability of each dose group were significantly lower than that of control group( P<0. 05). The expressions of Akt were significantly lower in iron and aluminum group,than that in control group( P< 0. 05). The expression of GSK-3β had no significant difference( P> 0. 05). The levels of phosphorylation of GSK-3β and Akt in all groups were significantly lower than those of control group( P<0. 05). With the concentration of copper,iron,zinc and aluminum increased,the apoptosis rates were significantly higher than that of control group( P<0. 05). Conclusions Copper,iron,zinc,aluminum could induce neurotoxicity,inhibit the activity of Akt,activate the glycogen synthase kinase 3βand lead to the neuronal apoptosis.更多还原