丙泊酚对谷氨酸诱导的PC12细胞凋亡的影响

来源 :中国临床药理学杂志 | 被引量 : 0次 | 上传用户:yanghao_haohao
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目的探讨丙泊酚对谷氨酸诱导的PC12细胞凋亡的影响。方法用10 mmol·L~(-1)谷氨酸损伤PC12细胞48 h,并分为模型组和丙泊酚低、中、高剂量组。取正常生长的PC12细胞作为对照组。对照组和模型组予以不含药物培养基培养48 h,丙泊酚低、中、高剂量组分别予以12.5,25.0,50.0μmol·L~(-1)丙泊酚培养48 h。通过噻唑蓝(MTT)法检测细胞活力,用流式细胞术检测细胞凋亡,用紫外分光光度法检测Caspase-3活性,用反转录聚合酶链式反应法和Western blot检测即刻早基因(c-fos)与早期生长反应因子基因-1(Egr-1)mRNA及蛋白水平。结果与对照组比较,模型组的细胞活力显著下降(P<0.01),凋亡率显著提高(P<0.01),Caspase-3活性显著上升(P<0.01),c-fos mRNA及蛋白水平显著下调(P<0.01),Egr-1 mRNA及蛋白水平显著上调(P<0.01)。与模型组比较,丙泊酚低、中、高剂量组的细胞活力显著提高(P<0.01),细胞凋亡率显著下降(P<0.01),Caspase-3活性显著降低(P<0.01),c-fos mRNA及蛋白水平显著上调(P<0.01),Egr-1 mRNA及蛋白水平显著下调(P<0.01)。结论丙泊酚可显著抑制谷氨酸诱导的PC12细胞凋亡,其作用机制与调节c-fos及Egr-1的表达有关。 Objective To investigate the effect of propofol on glutamate-induced PC12 cell apoptosis. Methods PC12 cells were injured by 10 mmol·L -1 glutamate for 48 h and divided into model group and low, medium and high dose propofol groups. The normal growth of PC12 cells as a control group. Control group and model group were cultured in drug-free medium for 48 h, propofol low, medium and high dose groups were cultured with propofol 12.5, 25.0, 50.0μmol·L -1 for 48 h. Cell viability was measured by MTT assay. Apoptosis was detected by flow cytometry. Caspase-3 activity was detected by UV spectrophotometry. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of immediate early gene c-fos) and early growth response factor 1 (Egr-1) mRNA and protein levels. Results Compared with the control group, the viability of the model group was significantly decreased (P <0.01), the apoptosis rate was significantly increased (P <0.01), the activity of Caspase-3 was significantly increased (P <0.01) (P <0.01), Egr-1 mRNA and protein levels were significantly increased (P <0.01). Compared with the model group, the cell viability of propofol low, medium and high dose groups was significantly increased (P <0.01), the apoptosis rate was significantly decreased (P <0.01), Caspase-3 activity was significantly decreased c-fos mRNA and protein levels were significantly increased (P <0.01), Egr-1 mRNA and protein levels were significantly decreased (P <0.01). Conclusion Propofol can significantly inhibit glutamate-induced PC12 cell apoptosis, and its mechanism of action is related to the regulation of c-fos and Egr-1 expression.
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