论文部分内容阅读
在早期工作发现小剂量亚硒酸钠 (Sodiumselenite)对离体皮质神经元的致凋亡作用的基础上 ,观察了在亚硒酸钠致凋亡模型中加入M型胆碱能受体激动剂Carbachol(Carb)能否阻止凋亡过程和相伴随的有关基因表达的改变。结果显示 :①用不同剂量 (0 .0 0 4 ,0 .0 2 ,0 .1,0 .5,2 .5和 12 .5mmol/L)的Carb和 0 .5μmol/L亚硒酸钠共同处理培养的新生小鼠皮质神经元时 ,用琼脂糖凝胶电泳DNA梯形检测和流式细胞仪亚二倍体峰检测 ,都证明Carb表现出对亚硒酸钠致凋亡作用的剂量依赖性保护效应 ;②用RT PCR技术证明 ,在与Carb共同孵育的实验中 ,不再出现或减弱了亚硒酸钠单独处理时出现的bcl 2基因表达的下调和bax ,p53,c fos以及AChE基因表达的上调。上述结果表明 ,亚硒酸钠对皮质神经元的致凋亡作用和与之相伴随的基因表达的改变 ,可被一定浓度的Carb所阻断 ,提示亚硒酸钠致凋亡作用可能同本室发现的 β 淀粉样蛋白的C末端 5肽片段的致凋亡作用具有类似的途径 ,以类似的基因表达改变为基础 ,并对Carb的抗凋亡机制进行了讨论。
In the early work found that small doses of sodium selenite induced apoptosis in isolated cortical neurons on the basis of the observed in sodium selenite induced apoptosis model M-type cholinergic receptor agonist Can Carbachol (Carb) block the process of apoptosis and the associated changes in gene expression? The results showed that: (1) Carb and 0.5μmol / L sodium selenite with different dosages (0. 0 0, 0 0,02,0.1,0.5,2.5 and 12.5 mmol / L) Treatment of cultured neonatal mouse cortical neurons with both agarose gel electrophoresis DNA ladder detection and flow cytometry sub-diploid peak detection demonstrated that Carb exhibited a dose-dependent apoptosis effect on sodium selenite ② The results of RT PCR showed that the down-regulation of bcl 2 gene expression and the expression of bax, p53, c fos and AChE gene no longer occurred or weakened in the treatment with Carb Up-regulation of expression. These results indicate that the apoptotic effect of sodium selenite on cortical neurons and the accompanying changes in gene expression can be blocked by a certain concentration of Carb, suggesting that the apoptosis induced by sodium selenite may be the same The apoptotic effects of the C-terminal 5-peptide fragment of beta-amyloid found in the ventricular compartment have similar pathways, based on similar gene expression changes and discussed the anti-apoptotic mechanisms of Carb.