牛蒡子苷元对阿尔茨海默病体外模型细胞凋亡和氧化损伤的影响

柯来顺 涂燕芬 林庆金 刘华斌 肖雪莲

摘要 目的：探討牛蒡子苷元对阿尔茨海默病体外模型β淀粉样肽25-35（Aβ25-35）诱导PC12细胞凋亡和氧化损伤的影响及机制。方法：将PC12细胞分成对照组、模型组（Aβ25-35处理）、ATG-L组（2 μmol/L牛蒡子苷元和Aβ25-35处理）、ATG-M组（4 μmol/L牛蒡子苷元和Aβ25-35处理）、ATG-H组（8 μmol/L牛蒡子苷元和Aβ25-35处理）、ATG-H+LY29400组（AKT信号抑制剂LY29400、8 μmol/L牛蒡子苷元和Aβ25-35处理）。以流式细胞术检测细胞凋亡变化，黄嘌呤氧化法检测超氧化物歧化酶（SOD）含量，Western Blotting法检测磷酸化的蛋白激酶B（p-AKT）蛋白表达。结果：ATG-L组、ATG-M组、ATG-H组p-AKT/AKT表达量以及SOD含量高于模型组，差异均有统计学意义（均P<0.05）;ATG-L组、ATG-M组、ATG-H组细胞凋亡率低于模型组，差异均有统计学意义（均P<0.05）;ATG-H+LY29400组p-AKT/AKT表达量以及SOD含量低于ATG-H组，差异均有统计学意义（均P<0.05）;ATG-H+LY29400组细胞凋亡率高于ATG-H组，差异均有统计学意义（均P<0.05）。结论：牛蒡子苷元通过激活AKT信号通路抑制阿尔茨海默病体外模型Aβ25-35诱导PC12细胞凋亡和氧化损伤。

关键词 牛蒡子苷元;PC12细胞;阿尔茨海默病;β淀粉样肽25-35;AKT信号;凋亡;氧化损伤;增殖

Abstract Objective：To investigate the effect and its mechanis of arctigenin on the apoptosis and oxidative damage of PC12 cells induced by amyloid beta 25-35（Aβ25-35）in an in vitro model of Alzheimer′s disease.Methods：PC12 cells were divided into a control group，a model group （Aβ25-35 treatment），a ATG-L group （2 μmol/L arctigenin and Aβ25-35 treatment），a ATG-M group （4 μmol/L arctigenin and Aβ25-35 treatment），a ATG-H group （8 μmol/L arctigenin and Aβ25-35 treatment），and a ATG-H+LY29400 group （AKT signal inhibitor LY29400，8 μmol/L arctigenin and Aβ25-35 treatment）.Flow cytometry was used to detect cell apoptosis changes.Xanthine oxidation method was used to detect superoxide dismutase （SOD） content.The expression of Phosphorylated protein kinase B （p-AKT） protein in cells was detected with Western Blotting method.Results：P-AKT/AKT expression and SOD content in the ATG-L，ATG-M，ATG-H group were higher than those in the Model group，and the differences were statistically significant （Ps<0.05）; The apoptosis rate of the ATG-L，ATG-M，ATG-H group were lower than those of the Model group，and the difference was statistically significant （Ps<0.05）; The p-AKT/AKT，SOD levels in the ATG-H+LY29400 group were lower than those in the ATG-L，ATG-M and ATG-H group，and the differences were statistically significant （Ps<0.05）; The apoptosis rate in the ATG-H+LY29400 group were higher than those in the ATG-H group，and the differences were statistically significant （Ps<0.05）.Conclusion：Arctigenin can inhibit the apoptosis and oxidative damage of PC12 cells induced by Aβ25-35 in an in vitro model of Alzheimer′s disease by activating the AKT signaling pathway.

Keywords Arctigenin; PC12 cells; Alzheimer′s disease; Aβ25-35; AKT signal; Apoptosis; Oxidative damage; Proliferation

中图分类号：R285;R745.1文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.22.010

阿尔茨海默病是一种常见的神经退行性疾病，也是常见的老年疾病之一，对于阿尔茨海默病发病机制，有氧化应激学说、瀑布假说、胆碱能学说、瀑布假说等多种学说[1]。β淀粉样肽（Amyloid Beta，Aβ）沉积诱导神经细胞损伤，促进神经功能障碍[2]。牛蒡子苷元是从中药牛蒡子中提取出来的活性成分，具有抗炎、抗病毒、调节免疫等作用，对肿瘤、糖尿病等有治疗功效[3-4]。有研究发现，牛蒡子苷元可改善神经功能，牛蒡子苷元处理可改善乙醇诱导的PC12细胞损伤，减少细胞凋亡[5]。……