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Protective effects of breviscapine against cultured rat hippocampal neuronal toxicity induced by glutamate
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- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 6
- DOI:
- 10.3321/j.issn:0513-4870.2007.06.003
- Key Word:
- 灯盏花素;谷氨酸;细胞凋亡;X-染色体连锁凋亡蛋白抑制因子;Ca2+
Abstract： 选用培养的海马神经细胞研究灯盏花素(breviscapine,Bre)对谷氨酸(glutamate,Glu)诱导神经细胞毒性的保护作用及其机制.新生大鼠海马神经细胞体外培养8 d后, 用L-谷氨酸(0.1, 0.5及1.0 mmol·L-1)处理30 min;灯盏花素处理组在加入L-谷氨酸的同时给予不同剂量的灯盏花素(10, 20及40 μmol·L-1);继续正常培养24 h后, 用Annexin V联合流式细胞仪检测细胞的凋亡和坏死率;RT-PCR分析凋亡蛋白抑制剂XIAP mRNA的表达.结果表明, L-谷氨酸浓度依赖性地诱导神经细胞发生凋亡和坏死, 并使细胞XIAP mRNA表达发生浓度依赖性的双向变化: 0.1 mmol·L-1 L-谷氨酸使神经细胞XIAP mRNA表达增强, 而较高浓度使XIAP mRNA表达下调.灯盏花素(20和40 μmol·L-1)可有效抑制谷氨酸诱导的神经细胞死亡, 分别使细胞凋亡率下降30.4%和40.1%, 坏死率下降32.5%和38.8%;并上调XIAP mRNA表达45.1%和54.9%.激光共聚焦显微技术联合Fluo-3荧光标记检测表明,L-谷氨酸处理过程中海马神经细胞内Ca2+水平显著升高, 而灯盏花素可抑制谷氨酸引起的细胞内Ca2+超载(P＜0.01).以上结果提示, 灯盏花素可能通过抑制细胞Ca2+超载, 调节凋亡抑制因子XIAP的表达而有效保护谷氨酸对神经细胞的兴奋性毒性作用.
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