远志皂苷元对Aβ_(1-42)诱导PC12细胞凋亡和自噬的影响  

Effects of Tenuigenin on Apoptosis and Autophagy in an Aβ_(1-42)-induced PC12 Cell

作　　者：陈玉静[1] 黄小波[1] 王倩[1] 孙亚男[1] 刘妍[1] 吴犀翎[1] CHEN Yujing;HUANG Xiaobo;WANG Qian;SUN Yanan;LIU Yan;WU Xiling(Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院北京市中西医结合老年疾病研究所,北京100053

出　　处：《中西医结合心脑血管病杂志》2023年第13期2418-2422,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：北京市中医药科技发展资金项目(No.JJ2018-22);北京市属医院科研培育计划项目(No.PZ2023009)。

摘　　要：目的:观察远志皂苷元(TEN)对阿尔茨海默病体外模型β-淀粉样蛋白1-42(Aβ_(1-42))诱导PC12细胞凋亡和自噬的影响。方法:体外培养PC12细胞,并随机分为对照组(正常生长PC12细胞)、模型组(Aβ_(1-42)诱导PC12细胞损伤)以及TEN低、中、高剂量组(Aβ_(1-42)诱导PC12细胞损伤+TEN低、中、高剂量)。采用四甲基偶氮唑蓝(MTT)法检测细胞存活率,流式细胞仪检测细胞凋亡,蛋白免疫印迹法(Western Blot)检测磷酸化磷脂酰肌醇-3-激酶(p-PI3K)、磷酸化蛋白激酶B(p-Akt)蛋白和自噬相关蛋白微管相关蛋白1轻链3Ⅱ(LC3-Ⅱ)和Beclin-1以及凋亡相关蛋白Caspase-3、Bcl-2和Bax的表达。结果:与对照组比较,模型组细胞活力明显下降(P<0.01),p-PI3K、p-Akt和Bcl-2蛋白表达明显降低(P<0.01),Caspase-3、Bax、LC3-Ⅱ和Beclin-1蛋白表达明显升高(P<0.01);与模型组比较,TEN各剂量组神经元存活率升高,p-PI3K、p-Akt和Bcl-2蛋白表达增加,Caspase-3、Bax、LC3-Ⅱ和Beclin-1蛋白表达减少,差异均有统计学意义(P<0.05或P<0.01)。结论:TEN有助于减轻Aβ_(1-42)诱导的PC12细胞毒性,其机制可能与抑制凋亡和自噬水平有关。Objective:To observe the effect of tenuigenin(TEN)on apoptosis and autophagy in an Aβ1-42-induced PC12 cell model of Alzheimer's disease.Methods:PC12 cells were cultured in vitro,and randomly divided into control group(normal growth of PC12 cells),model group(Aβ1-42 induced PC12 cell damage),and low-dose,medium-dose,and high-dose TEN groups(Aβ1-42 induced PC12 cell damage+low-dose,medium-dose,and high-dose TEN)respecively.Methyl thiazolyl tetrazolium(MTT)assay was used to detect the cell survival rate.Apoptosis was detected by flow cytometry.Western Blot was used to detect the expression of phosphorylated phosphatidylinosito-l 3-kinase(p-PI3K),phosphorylated protein kinase(p-Akt),microtubule-associated protein 1 light chain 3(LC3-Ⅱ),Beclin-1,and apoptosis-related proteins Caspase-3,Bc-l 2,and Bax.Results:Compared with control group,the survival rate of the model cells was significantly decreased(P<0.01),the protein expressions of p-PI3K,p-Akt,and Bc-l 2 were significantly down-regulated,while the protein expressions of Caspase-3,Bax,LC-3Ⅱ,and Beclin-1 were significantly up-regulated(P<0.01)in model group.Compared with model group,the survival rate of neurons was increased,the protein expressions of p-PI3K,p-Akt,and Bc-l 2 were increased,and the protein expressions of Caspase-3,Bax,LC3-Ⅱ,and Beclin-1 were decreased(P<0.05 or P<0.01)in all doses of TEN groups.Conclusion:TEN can rduce the cytotoxicity of PC12 induced by Aβ1-42,and its mechanism may be related to the inhibition of apoptosis and autophagy levels.

关 键 词：阿尔茨海默病 远志皂苷元 β-淀粉样蛋白1-42 细胞凋亡 自噬 实验研究 

分 类 号：R285[医药卫生—中药学]