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氯化铝对大鼠皮层神经元凋亡及bc1-2、bax基因表达的影响

Effects of aluminum chloride on the apoptosis and the expression of bc1-2 and bax genes in rat cortical neurons

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【作者】 傅洪军; 董胜璋; 任铁玲; 林忠宁;

【Author】 FU Hong\|jun, DONG Sheng\|zhang, REN Tie\|ling, et al. (Faculty of Preventive Medicine, School of Public Health, Sun Yat\|sen University, Guangzhou Guangdong 510080,China)

【机构】 中山大学公共卫生学预防医学系; 中山大学公共卫生学预防医学系 广东广州510080; 广东广州510080; 广东广州510080;

【摘要】 目的 探讨氯化铝 (AlCl3)对大鼠皮层神经元凋亡的诱导作用及对bc1 2、bax基因表达的影响。方法 体外原代无血清培养至第 7天的大鼠皮层神经元 ,实验组的培养液中加入AlCl3(终浓度分别为 10、10 0、10 0 0 μmol L) ,对照组的培养液中加入等体积分数为 0 9%的生理盐水 ,培养 48h后 ,用原位末端标记法 (TUNEL)测定其细胞凋亡率 ;培养 2 4h后 ,用RT PCR法检测bc1 2、bax基因的表达。结果 各染铝组大鼠皮层神经元凋亡率明显升高 ,与对照组相比 ,差异有显著性 (P <0 0 5 ) ,并具有明显的剂量 反应关系 ;bc1 2基因表达明显下降 ,bax基因表达明显升高 ,bc1 2 bax逐渐下降 ,与对照组相比 ,差异有显著性 ,也具有明显的剂量 反应关系。相关分析表明 ,大鼠皮层神经元凋亡率与bc1 2基因表达呈负相关 ,与bax基因表达呈正相关 ,而与bc1 2 bax呈负相关 (P <0 0 1)。结论 铝可以诱导大鼠皮层神经元凋亡 ,其机制可能与bc1 2基因表达下调 ,bax基因表达上调以及bc1 2 bax下降有关。

【Abstract】 Objective To explore the effects of aluminum chloride (AlCl\-3) on the apoptosis in rat cortical neurons and the relationship between the apoptosis and the expression of the bc1\|2 as well as bax gene. Methods After cortical neurons were cultured for 6 days, AlCl\-3 was given to cultured neurons at the dosage of(0,10,100,1000)μmol/L. Cortical neurons were incubated with AlCl\-3 for 48 hours, then measured the rates of apoptosis with the method of TdT\|mediated dUTP nick end labeling (TUNEL). The expression of bc1\|2 and bax was measured by RT\|PCR after cortical neurons were incubated with AlCl\-3 for 24 hours. Results The rates of apoptosis in cortical neurons in every treatment group were significantly higher than that of control ( P< 0 05), and there was a significant dose\|response relationship ( r=0 823,P<0 01 ). The expression of bc1\|2 was significantly decreased, whereas bax was significantly increased, in cortical neurons in every aluminum chloride treatment group compared with the control group ( P <0 05), and there was a significant dose\|response relationship ( r =-0 809,0 867 respectively for bc1\|2 and bax, P <0 01). The value of bc1\|2/bax in every treatment group decreased significantly compared with control, and there was a significant dose\|response relationship ( r =-0 790, P <0 01). Correlation analysis showed that the rates of apoptosis were inversely correlated with the expression of bc1\|2 ( r =-0 927, P <0 01), whereas positively correlated with the expression of bax ( r =0 891, P <0 01). And there were inverse correlations between the rates of apoptosis and bc1\|2/bax expression ( r=-0 931,P<0 01 ).Conclusion Aluminum may induce apoptosis in rat cortical neurons through the down regulation of bc1\|2 and the up regulation of bax gene expression.

【关键词】 铝; 皮层神经元; 凋亡; Bc12基因; bax基因;
【Key words】 Aluminum chloride; Cortical neurons; Apoptosis; Bc1\|2 gene; Bax gene;
【基金】 中华医学基金会 (CMB)资助课题 (91549)
  • 【文献出处】 卫生毒理学杂志 ,Journal of Health Toxicology , 编辑部邮箱 ,2003年01期
  • 【分类号】R114
  • 【被引频次】40
  • 【下载频次】169
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