【摘要】 目的探讨钙信号在2,2’,4,4’-四溴联苯醚(2,2’,4,4-’tetrabromodiphenyl ethers,PBDE-47)和2,2’4,4’,5,5’六氯联苯(2,2’,4,4’,5,5-’hexachlorobiphenyl,PCB153)诱导人神经母细胞瘤细胞株SH-SY5Y细胞凋亡中的作用。方法PBDE-47设3个剂量组(1、5、10μmol/L),PCB153设1个剂量组(5μmol/L),DMSO为溶剂对照组,PBDE-47与PCB153单独和联合染毒SH-SY5Y细胞24 h后,检测细胞存活率、胞内钙离子浓度[Ca2+]i、细胞凋亡率和Caspase3、Caspase12、Cytochrome C及死亡相关蛋激酶(DAPK)等钙信号通路相关基因mRNA表达水平。结果与溶剂对照组相比,5、10μmol/LPBDE-47染毒剂量组细胞存活率均显著下降,差异有统计学意义(P<0.05);与对照组相比,1、5、10μmol/L PBDE-47剂量组[Ca2+]i和细胞凋亡率均显著增加(P<0.05)。PCB153可明显增加PBDE-47诱导的[Ca2+]i和细胞凋亡率,并存在交互作用(F=6.642,P<0.01;F=10.226,P<0.01)。与对照组相比,PBDE-47可使上述基因mRNA表达水平均增强(P<0.05)。PBDE-47和PCB153联合对Cytochrome C和Caspase3 mRNA表达水平的影响均存在交互作用(P<0.05)。结论钙信号可通过3条经典凋亡通路参与PBDE-47诱导SH-SY5Y细胞的凋亡,PBDE-47和PCB153在诱导SH-SY5Y细胞凋亡过程中存在交互作用。更多还原

【Abstract】 Objective To study the effect of Ca²⁺ signalling on apoptosis induced by 2,2’,4,4’-tetrabromodiphenyl ethers（PBDE-47） and 2,2’,4,4’,5,5’-hexachlorobiphenyl（PCB153） in SH-SY5Y cells.Methods SH-SY5Y cells were treated with PBDE-47 at different concentrations（1,5,10 μmol/L） or/and PCB153（5 μmol/L） for 24 h.DMSO was used as solvent control.The cell Viabilities,Intracellular calcium concentration([Ca²⁺]i),percent of apoptotic cells,and mRNA expression levels of DAPK,Caspase3,Caspase12 and Cytochrome C were detected,respectively.Results Compared with the solvent control,the cell viabilities were notably decreased at 5 and 10 μmol/L PBDE-47-treated groups（P<0.05）;Compared with the solvent control,the [Ca²⁺]_i and percent of apoptotic cells were significantly increased at 1,5 and 10 μmol/L PBDE-47-treated groups（P<0.05）.The interaction existed between PBDE-47 and PCB153 in increasing [Ca²⁺]_i and percent of apoptotic cells （F=6.642,P<0.01 and F=10.226,P<0.01,respectively）,and there was a positive correlation between [Ca²⁺]_i and percent of apoptotic cells（r=0.86,P<0.05）. Compared with the solvent control,the mRNA expression levels of DAPK,Caspase3,Caspase12 and Cytochrome C were significantly increased in all PBDE-47-treated groups（P<0.05）.The interaction existed between PBDE-47 and PCB153 in influencing the mRNA expression levels of Cytochrome C and Caspase3（P<0.05）.Conclusions Ca²⁺ signalling participated the course of apoptosis induced by PBDE-47 in SH-SY5Y cells via three classic apoptosis pathways.There was an interaction between PBDE-47 and PCB153 in inducing SH-SY5Y cells apoptosis.更多还原