摘要
目的研究丁基苯酞是否可以通过p38丝裂原活化蛋白激酶(MAPK)信号通路,抑制β淀粉样蛋白(Aβ)_(1 42)致原代培养皮质神经元凋亡。方法将原代培养的皮质神经元随机分为对照组、Aβ_(1-42)干预组(干预组)、Aβ_(1-42)+丁基苯酞0.1μmol/L组(A组)、Aβ_(1-42)+丁基苯酞1μmol/L组(B组)、Aβ_(1 42)+丁基苯酞10μmol/L组(C组)。Aβ_(1-42)作用24 h后,采用免疫荧光法染色观察细胞形态及凋亡比率,Western blot定量检测总p38、p-p38、caspase 3蛋白表达水平。结果免疫荧光双染显示,对照组神经元细胞体边缘光滑,突触长,细胞核完整;干预组细胞边缘塌陷,突触缩短,细胞核碎裂。与对照组比较,干预组、A、B、C组细胞凋亡率明显升高(P<0.05),干预组p p38和caspase-3蛋白表达明显增加(P<o.05);与干预组比较,A、B、C组caspase 3蛋白表达及B、C组p p38蛋白表达明显减少(P<0.05)。结论丁基苯酞可以通过p38蛋白磷酸化拮抗Aβ_(1-42)致原代培养皮质神经元凋亡。
Objective To elucidate the mechanism of L-3-n-butylphthalide protect against Aβ1-42-in- duced apoptosis of cultured primary cortical neuron through p38 mitogen activated protein kinase (MAPK) pathway. Methods After pretreatment with L-3-n-butylphthalide of differernt concentrations(0.1,1,10μmol/L) for 4 h before exposure to Aβ1-42 (10 μmol/L) for 24 h. Changes of cell morphology was observed and the apoptotic rate was determined by an inverted fluorescence microscope,Expression of target proteins (total p38, phosph-p38, caspase-3) was determined by Western blot. Results After exposure to Aβ1-42 for 24 h,cell apoptotic rate remarkably increased, expression of p-p38 and caspase-3 increased (P 〈0.05). Pretreatment with L 3-n-butylphthalide for 4 h could significantly inhibit the AI3H2 induced apoptotic rate increase, and signifcantly inverted the increased expression of p-p38 and caspase-3 (P〈0.05). Conclusion L-3 n-butylphthalide could protect Alzheimer disease neurons through decreasing p38 MAPK phosphorylation.
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2011年第8期750-753,共4页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
山东省医药卫生科技发展计划(2007HZ065)