丙戊酸钠对Aβ25~35诱导PC12细胞损伤的影响  

Effect of valproate on PC12 cell injury induced by Aβ25~35

作　　者：徐晨阳 丁炳谦 高明 李振江 苑兵舰 XU Chen-Yang;DING Bing-Qian;GAO-Ming(Department of Neurosurgery,Huaihe Hospital of Henan University,Kaifeng 475000,Henan,China)

机构地区：[1]河南大学淮河医院神经外科,河南开封475000

出　　处：《中国老年学杂志》2020年第20期4393-4396,共4页Chinese Journal of Gerontology

基　　金：河南省科技发展计划项目(182102311180)。

摘　　要：目的探讨丙戊酸钠(VPA)对β淀粉样蛋白(Aβ25~35)诱导的PC12细胞损伤的影响。方法将PC12细胞随机分为正常组,Aβ25~35组(20μmol/L的Aβ25~35),VPA低、中、高剂量组(2.5、5.0,10.0μmol/L VPA+20μmol/L的Aβ25~35)。噻唑蓝(MTT)法检测细胞活力,流式双染检测细胞凋亡,比色法检测含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)3、Caspase9活性,Western印迹检测各组细胞中B细胞淋巴瘤/白血病(Bcl)-2、Bcl-2相关X蛋白(Bax)、磷脂酰肌醇-3-羟激酶/蛋白激酶B/糖原合成酶激酶3β(PI3K/AKT/GSK3β)信号通路激活情况。结果与正常组比较,Aβ25~35组细胞活力显著降低(P<0.01),细胞凋亡率、Caspase3、Caspase9活性显著提高(P<0.01),Bax、p-GSK3β表达量显著上调(P<0.01),Bcl-2、PI3K、p-AKT表达量显著下调(P<0.01)。与Aβ25~35组比较,VPA低、中、高剂量组细胞活力显著提高(P<0.01),细胞凋亡率、Caspase3、Caspase9活性显著降低(P<0.01),Bax表达量显著下调(P<0.01),Bcl-2、p-AKT表达量显著上调(P<0.01),VPA中、高剂量组细胞中p-GSK3β表达量显著下调(P<0.01),PI3K表达量显著上调(P<0.01)。结论VPA可能通过抑制PI3K/AKT/GSK3β信号通路抵抗Aβ25~35诱导的PC12细胞凋亡。Objective To explore effect of valproate(VPA)on PC12 cell injury induced by Aβ25~35.Methods PC12 cells were randomly divided into normal control,Aβ25~35(20μmol/L Aβ25~35),VPA low,medium and high concentration group(2.5,5.0,20.0μmol/L VPA+20μmol/L Aβ25~35).Cell viability was measured by MTT assay.Cell apoptosis was measured by flow cytometry.The activity of Caspase3 and Caspase9 were detected by colorimetry.The expressions of B-cell lymphoma/leukemia(Bcl)-2,Bcl-2-related X protein(Bax),the activation of phosphatidylinositol-3-hydroxylkinase/protein kinase B/glycogen synthase kinase 3 beta(PI3K/AKT/GSK3β)signal pathway was detected by Western blot.Results Compared with normal group,cell viability was reduced significantly(P<0.01),cell apoptotic rate,Caspase3 and Caspase9 activity were increased significantly(P<0.01),the expressions of Bax and p-GSK3βwere up-regulated significantly(P<0.01),the expression of Bcl-2,PI3K and p-AKT were significantly down-regulated in Aβ25~35 group(P<0.01).Compared with Aβ25~35 group,cell viability was increased significantly(P<0.01),cell apoptotic rate,Caspase3 and Caspase9 activity were decreased significantly(P<0.01),the expression of Bax was down-regulated significantly(P<0.01),the expression of Bcl-2 and p-AKT were significantly up-regulated in VPA low,medium and high concentration group(P<0.01),the expression of PI3K was significantly up-regulated,the expression of p-GSK3βwas significantly down-regulated in VPA medium and high concentration groups(P<0.01).Conclusions Low concentration of VPA could resist PC12 cells apoptosis induced by Aβ25~35 via inhibiting the PI3K/AKT/GSK3βsignaling pathway.

关 键 词：丙戊酸钠(VPA) PC12细胞 凋亡 磷脂酰肌醇-3-羟激酶/蛋白激酶B/糖原合成酶激酶3β信号通路 

分 类 号：R285.5[医药卫生—中药学]