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目的:探讨嘌呤霉素敏感的氨肽酶(PSA)对TauP301L诱导的细胞凋亡的影响。方法将TauP301L表达载体转入SH-SY5Y和PC12细胞24、48和72 h后,采用MTT法检测两种细胞增殖率的变化,Hoechst33342染色检测细胞核形态学的变化,确定TauP301L的最佳作用时间;在PC12细胞中转染TauP301L和PSA载体,在SH-SY5Y细胞中转染TauP301L和PSA-siRNA载体,Western blotting法检测Caspase-3的表达,酶标仪检测Caspase-3的活性变化,流式细胞法检测细胞凋亡率。结果 TauP301L诱导细胞凋亡具有时间依赖性。 TauP301L转染细胞48 h后,PC12细胞、SH-SY5Y细胞存活率明显下降(P<0.01),细胞核出现凋亡的形态学变化;流式检测细胞凋亡率增加(P<0.01)。在PC12细胞中,与TauP301L组相比,PSA和TauP301L共同作用组Caspase-3的活性形式表达量及酶活性明显下降(P<0.01),细胞凋亡率显著下降(P<0.01);而在SH-SY5Y细胞中,与TauP301L组相比,TauP301L和PSA-siRNA共同作用组的细胞凋亡率显著升高(P<0.05),Caspase-3的活性形式表达量和活性均升高(P<0.01)。结论 TauP301L能够诱导细胞凋亡,而PSA能够下调TauP301L所诱导的这种凋亡,对神经细胞起到保护作用。“,”Objective To explore the effect of puromycin-sensitive aminopeptidase ( PSA) on the apoptosis induced by TauP301L in SH-SY5Y cells and PC12 cells.Methods The proliferation and morphological changes of the cells were de-tected after SH-SY5Y and PC12 cells were transfected with TauP301L for 24, 48 and 72 h, respectively.The optimal time for TauP301L transfection was determined.To evaluate the effect of PSA on cell apoptosis, PC12 cells were transfected with PSA and TauP301L , and SH-SY5Y cells were transfected with PSA-siRNA and TauP301L .Cell apoptosis was deter-mined by flow cytometry.The expression and activity of Caspase-3 were detected by Western blotting and Microplate reader, respectively.Results TauP301L induced cells apoptosis in a time-dependent manner.After TauP301L transfection for 48 h, the proliferations of SH-SY5Y and PC12 cells significantly decreased (P<0.01), while the apoptosis of the cells increased (P <0.01), as well as apoptosis-like cells could be found after Hoechst33342 staining of cell nuclei. Compared with TauP301L transfection, the expression and activity of Caspase-3 were downregulated (P<0.01), and theapoptosis decreased (P<0.01) after transfection with both PSA and TauP301L in PC12 cells.However, the expression and activity of Caspase-3 were upregulated (P<0.01) and the apoptosis increased (P<0.05) after transfection with both PSA-siRNA and TauP301L in SH-SY5Y cells.Conclusion TauP301L can induce apoptosis in both SH-SY5Y cells and PC12 cells.PSA has a protective effect on nerve cells by inhibiting apoptosis induced by TauP301L .