Aβ_(25-35)对大鼠大脑皮质神经元神经甾体水平的影响  

Effect of Aβ_(25-35) on neurosteroidogenesis in primary rat cortical neurons

作　　者：于洋[1,2] 薛改[2] 吴红海[2] 李莎莎[1,2] 侯艳宁[1,2] 

机构地区：[1]河北医科大学药理学教研室,河北石家庄050017 [2]中国人民解放军白求恩国际和平医院药学部,河北石家庄050082

出　　处：《中国药理学通报》2010年第6期783-786,共4页Chinese Pharmacological Bulletin

摘　　要：目的研究Aβ25-35对大鼠大脑皮质神经元合成神经甾体的影响。方法采用Aβ25-35(1μmol·L-1)处理原代培养的大鼠大脑皮质神经元,固相萃取结合高效液相色谱-质谱联用法测定细胞培养液中神经甾体的浓度,四甲基偶氮唑(MTT)法检测细胞活性。结果与对照组相比,Aβ25-35处理后神经元存活率降低约50%(P<0.01),胆固醇处理组神经元存活率未见改变(P>0.05),但Aβ+胆固醇组的神经元存活率明显高于Aβ处理组(P<0.01)。与胆固醇组相比,Aβ25-35处理后神经甾体PREG水平略有降低(P>0.05),PROG水平明显下降(P<0.01),AP水平明显增高(P<0.01)。结论神经甾体PREG-PROG-AP代谢通路在Aβ25-35引起的大鼠大脑皮质神经元损伤时发生明显改变,并能部分地对抗Aβ的神经毒性作用。Aim To investigate the effect of Aβ25-35 on the neurosteroidogenesis in primary rat cortical neurons.Methods Primary cultured rat cortical neurons were treated with Aβ25-35（1 μmol·L-1）,and the concentrations of pregnenolone（PREG）,dehydroepiandrosterone（DHEA）,progesterone（PROG）and allopregnanolone（AP）were measured by LC-MS after solid-phase extraction.The neurons viability was determined as surviving rate by MTT.Results Compared with the control group,the neurons viability was reduced significantly to about 50%（P0.01）after being treated with Aβ25-35.The neurons viability was not affected by cholesterol treatment.While treated with Aβ25-35 simultaneously,cholesterol augmented the neurons viability to about 80%（P0.01）,possibly by being metabolized to neurosteroids.Compared with the cholesterol treatment group,when treated with Aβ25-35,PREG level reduced slightly,and PROG level reduced significantly（P0.01）,while AP level greatly increased（P0.01）.Conclution The present study firstly shows that neurosteroidogenesis in primary rat cortical neurons change greatly when treated with Aβ25-35,especially the PREG-PROG-AP pathway.Cholesterol,the necessary substrate for neurosteroidogenesis,can be partially against the Aβ25-35 neurotoxicity on cortical neurons.

关 键 词：Β-淀粉样蛋白 神经甾体发生 液相色谱-质联用法 皮质神经元 神经毒性 阿尔采末病 

分 类 号：R-332[医药卫生] R322.81