乌帕替尼对氧糖剥夺/复氧后BV2细胞极化的影响
投稿时间:2020-12-03  修订日期:2021-02-26  点此下载全文
引用本文:宋志兵,张倩,章越凡,邱彦,李铁军.乌帕替尼对氧糖剥夺/复氧后BV2细胞极化的影响[J].药学实践杂志,2021,39(2):112~117
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作者单位E-mail
宋志兵 安徽中医药大学药学院安徽 合肥 230012
上海市浦东新区浦南医院药剂科上海 200125 
 
张倩 安徽中医药大学药学院安徽 合肥 230012
上海市浦东新区浦南医院药剂科上海 200125 
 
章越凡 海军军医大学药学院药理学教研室上海 200433  
邱彦 上海市浦东新区人民医院上海 201200  
李铁军 安徽中医药大学药学院安徽 合肥 230012
上海市浦东新区浦南医院药剂科上海 200125 
ltj204@163.com 
基金项目:浦东新区卫生系统学科建设项目(新兴、交叉学科-精准临床药学,PWXx2020-03);浦东新区卫生和计划生育委员会学科建设项目(重要薄弱学科-临床药学,PWZbr2017-16);上海市健康医学院协同创新重大专项(SPCI-18-13-001)
中文摘要:目的 研究乌帕替尼对氧糖剥夺再复氧(OGD/R)后BV2小胶质细胞极化及炎症的影响,并探讨其作用机制。方法 实验分对照组、OGD组和乌帕替尼组3组。BV2细胞经OGD/R处理后,噻唑蓝试剂(MTT)检测细胞生存率,划痕实验观察细胞迁移能力,实时荧光定量多聚核苷酸链式反应(qPCR)检测BV2细胞M1型极化标志物(CD11b、CD32、iNOS)和M2型极化标志物(Arg-1、IL-10、CD206)的mRNA水平,酶联免疫吸附测定(ELISA)检测培养基中IL-1β、IL-6、TNF-α含量,蛋白质印迹法(Western Blot)检测JAK1/STAT6通路相关蛋白表达水平。结果 乌帕替尼能增加OGD/R后BV2细胞的生存率(P<0.05),能减少BV2细胞向M1型极化(P<0.05)。乌帕替尼可明显降低OGD/R诱导的BV2细胞的迁移能力(P<0.05),减少OGD/R诱导BV2细胞分泌的炎症因子:IL-1β、IL-6、TNF-α(P<0.05)。乌帕替尼提高共培养PC12细胞的生存率(P<0.05)。乌帕替尼可显著抑制由OGD/R诱导激活BV2细胞p-JAK1和p-STAT6蛋白的表达水平(P<0.05)。结论 乌帕替尼可减少OGD/R诱导BV2细胞向M1型极化和减少炎症反应,与JAK1/STAT6通路有关。
中文关键词:乌帕替尼  氧剥夺/复氧  极化,炎症,酪氨酸激酶/信号传导及转录激活因子
 
Effects of upadacitinib on BV2 cells after oxygen–glucose deprivation/recovery
Abstract:Objective To investigate the effects of upadacitinib on the polarization and inflammation of BV2 microglia after oxygen glucose deprivation/recovery (OGD/R) and to explore its mechanism of action.Methods The experiment was divided into 3 groups: control group, OGD group and upadacitinib treatment group. After BV2 cells were treated with OGD/R, MTT was used to detect cell survival rate. Wound scratch assay was used to detect the cell migration ability. qPCR was used to detect mRNA levels of M1-type polarization markers (CD11b, CD32, iNOS) and M2-type polarization markers (Arg-1, IL-10, CD206) of BV2 cells. ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in the culture medium. Western blot was used to detect the expression levels of JAK1/STAT6 pathway-related proteins.Results Upadacitinib increased the survival of BV2 cells after OGD/R (P<0.05), reduced the polarization of BV2 cells to M1 type (P<0.05). Upadacitinib significantly decreased the migration ability of BV2 cells induced by OGD/R (P<0.05), reduced the inflammatory factors secreted by BV2 cells induced by OGD/R: IL-1β, IL-6, TNF-α (P<0.05). Upadacitinib increased the survival rate of co-cultured PC12 cells (P<0.05). Upadacitinib significantly inhibited the expression levels of p-JAK1 and p-STAT6 proteins in BV2 cells activated by OGD/R induction (P<0.05).Conclusion Upadacitinib decreases polarization of BV2 induced by OGD/R to M1 type and reduces inflammation, which is related to JAK1/STAT6 pathway.
keywords:upadacitinib  OGD/R  polarization, inflammation, JAK/STAT
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