抑制PI3K/AKt信号通路对帕金森病相关基因Nurr1表达的影响  

Effect of inhibition of PI3K/AKt signaling pathway on Parkinson′s disease-related Nurr1 gene expression

作　　者：庞霖霖 欧阳强[1] 韦宁[1] 钟才[1] 刘亚媛 周少旦 吕庚珉 何荣新 闫灵婉 PANG Lin-Lin;OUYANG Qiang;WEI Ning(Department of Neurology,MinZu Hospital of Guangxi Zhuang Autonomous Region,Nanning 530001,Guangxi,China)

机构地区：[1]广西壮族自治区民族医院广西医科大学附属民族医院神经内科

出　　处：《中国老年学杂志》2019年第15期3764-3767,共4页Chinese Journal of Gerontology

基　　金：崇左市研究与技术开发计划项目(崇科攻1324001)

摘　　要：目的探讨LY294002(LY)抑制磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKt)信号通路对帕金森病(PD)相关基因Nurr1表达的影响。方法体外培养BV2小胶质细胞,分为正常对照组、脂多糖(LPS)组、LY+LPS组及LY组。Western印迹检测各组PI3K/AKt信号通路标志物P-AKt蛋白表达情况;LY抑制PI3K/AKt信号通路后,运用荧光定量(Q)-PCR检测抗炎因子白细胞介素(IL)-4、转化生长因子(TGF)-β的mRNA及PD相关基因Nurr1的表达情况,CCK-8法检测各组细胞培养液对PC12细胞存活率的影响。结果与正常对照组相比,LPS组P-AKt蛋白表达显著下降(P<0.01);与LPS组相比,LY+LPS组下降更明显(P<0.01)。与对照组相比,LPS处组IL-4、TGF-β及Nurr1mRNA表达均显著升高(均P<0.01);与LPS组相比,LY+LPS组均显著升高(均P<0.01)。与正常对照组相比,LPS培养液培养的PC12细胞存活率显著下降(P<0.01),LY预处理可以抑制LPS导致的PC12细胞死亡率。结论LY抑制PI3K/AKt信号通路能够促进BV2中PD相关基因Nurr1的表达,且对LPS诱导的炎症反应有一定的抗炎作用。Objective To investigate the effects of PI3K/AKt signaling pathway inhibited by LY294002 on the expression of Parkinson′s disease-related Nurr1 gene.Methods The BV2 microglial was routinely cultured in vitro and experiment was divided into control,lipopolysaccharide(LPS),LY294002(LY)+LPS and the LY groups.Western blot was used to detect expression of P-AKt protein,which was the marker of PI3K/AKt signaling pathway.PI3K/AKt signaling pathway was inhibited by LY294002,real time quantitative PCR was used to detect the expression of anti-inflammatory factor IL-4,TGF-beta and Nurr1.CCK 8 method was used to detect the effects of each cell culture′s on PC12 cell survival rate.Results(1)Compared with normal control group,the expression of P-AKt protein expression was decreased induced by LPS(P<0.01);compared with LPS group,the expression of P-AKt protein decreased more significantly induced by LY294002+LPS(P<0.01).(2)Compared with control group,the expressions of IL-4,TGF-beta and Nurr1 mRNA were increased induced by LPS(all P<0.01);compared with LPS group,the expressions of IL-4,TGF-beta and Nurr1 mRNA were increased induced LY294002+LPS(P<0.01).(3)Compared with normal control group,the survival rate of PC12 cell was decreased after using culture containning LPS(P<0.01),LY294002 pretreatment could inhibit the mortality of PC12 caused by LPS.Conclusions LY294002 inhibiting PI3K/AKt signaling pathway could promote the expression of Nurr1 gene and has certain anti-inflammatory effects on inflammation induced by LPS.

关 键 词：PI3K/AKT信号通路 帕金森病 NURR1 炎症 PC12 

分 类 号：R741.05[医药卫生—神经病学与精神病学]